Important note: This answer was written in 2011, a few years before masterwok's answer was written. Whilst my answer is still acceptable, masterwok's answer is better and more concise. Use and upvote that answer instead. Everything below is for posterity.
I would just use the file extension rather than try to do something clever that may eventually come back to bite you in the arse. :)
The file extension doesn't need to be registered on your system (although I don't know exactly what you're doing with the file...). You could use something like an enum or db table which contains information on acceptable extensions if you want to filter out files.
Please see @Tolgahan's idea on this. I created a C# enum below based on this which should provide people with a starting point should they wish to create a db/enum/xml-based approach to this.
Public enum MimeTypes
{
[Description("application/postscript")]
ai,
[Description("audio/x-aiff")]
aif,
[Description("audio/x-aiff")]
aifc,
[Description("audio/x-aiff")]
aiff,
[Description("text/plain")]
asc,
[Description("application/atom+xml")]
atom,
[Description("audio/basic")]
au,
[Description("video/x-msvideo")]
avi,
[Description("application/x-bcpio")]
bcpio,
[Description("application/octet-stream")]
bin,
[Description("image/bmp")]
bmp,
[Description("application/x-netcdf")]
cdf,
[Description("image/cgm")]
cgm,
[Description("application/octet-stream")]
class,
[Description("application/x-cpio")]
cpio,
[Description("application/mac-compactpro")]
cpt,
[Description("application/x-csh")]
csh,
[Description("text/css")]
css,
[Description("application/x-director")]
dcr,
[Description("video/x-dv")]
dif,
[Description("application/x-director")]
dir,
[Description("image/vnd.djvu")]
djv,
[Description("image/vnd.djvu")]
djvu,
[Description("application/octet-stream")]
dll,
[Description("application/octet-stream")]
dmg,
[Description("application/octet-stream")]
dms,
[Description("application/msword")]
doc,
[Description("application/xml-dtd")]
dtd,
[Description("video/x-dv")]
dv,
[Description("application/x-dvi")]
dvi,
[Description("application/x-director")]
dxr,
[Description("application/postscript")]
eps,
[Description("text/x-setext")]
etx,
[Description("application/octet-stream")]
exe,
[Description("application/andrew-inset")]
ez,
[Description("image/gif")]
gif,
[Description("application/srgs")]
gram,
[Description("application/srgs+xml")]
grxml,
[Description("application/x-gtar")]
gtar,
[Description("application/x-hdf")]
hdf,
[Description("application/mac-binhex40")]
hqx,
[Description("text/html")]
htm,
[Description("text/html")]
html,
[Description("x-conference/x-cooltalk")]
ice,
[Description("image/x-icon")]
ico,
[Description("text/calendar")]
ics,
[Description("image/ief")]
ief,
[Description("text/calendar")]
ifb,
[Description("model/iges")]
iges,
[Description("model/iges")]
igs,
[Description("application/x-java-jnlp-file")]
jnlp,
[Description("image/jp2")]
jp2,
[Description("image/jpeg")]
jpe,
[Description("image/jpeg")]
jpeg,
[Description("image/jpeg")]
jpg,
[Description("application/x-javascript")]
js,
[Description("audio/midi")]
kar,
[Description("application/x-latex")]
latex,
[Description("application/octet-stream")]
lha,
[Description("application/octet-stream")]
lzh,
[Description("audio/x-mpegurl")]
m3u,
[Description("audio/mp4a-latm")]
m4a,
[Description("audio/mp4a-latm")]
m4b,
[Description("audio/mp4a-latm")]
m4p,
[Description("video/vnd.mpegurl")]
m4u,
[Description("video/x-m4v")]
m4v,
[Description("image/x-macpaint")]
mac,
[Description("application/x-troff-man")]
man,
[Description("application/mathml+xml")]
mathml,
[Description("application/x-troff-me")]
me,
[Description("model/mesh")]
mesh,
[Description("audio/midi")]
mid,
[Description("audio/midi")]
midi,
[Description("application/vnd.mif")]
mif,
[Description("video/quicktime")]
mov,
[Description("video/x-sgi-movie")]
movie,
[Description("audio/mpeg")]
mp2,
[Description("audio/mpeg")]
mp3,
[Description("video/mp4")]
mp4,
[Description("video/mpeg")]
mpe,
[Description("video/mpeg")]
mpeg,
[Description("video/mpeg")]
mpg,
[Description("audio/mpeg")]
mpga,
[Description("application/x-troff-ms")]
ms,
[Description("model/mesh")]
msh,
[Description("video/vnd.mpegurl")]
mxu,
[Description("application/x-netcdf")]
nc,
[Description("application/oda")]
oda,
[Description("application/ogg")]
ogg,
[Description("image/x-portable-bitmap")]
pbm,
[Description("image/pict")]
pct,
[Description("chemical/x-pdb")]
pdb,
[Description("application/pdf")]
pdf,
[Description("image/x-portable-graymap")]
pgm,
[Description("application/x-chess-pgn")]
pgn,
[Description("image/pict")]
pic,
[Description("image/pict")]
pict,
[Description("image/png")]
png,
[Description("image/x-portable-anymap")]
pnm,
[Description("image/x-macpaint")]
pnt,
[Description("image/x-macpaint")]
pntg,
[Description("image/x-portable-pixmap")]
ppm,
[Description("application/vnd.ms-powerpoint")]
ppt,
[Description("application/postscript")]
ps,
[Description("video/quicktime")]
qt,
[Description("image/x-quicktime")]
qti,
[Description("image/x-quicktime")]
qtif,
[Description("audio/x-pn-realaudio")]
ra,
[Description("audio/x-pn-realaudio")]
ram,
[Description("image/x-cmu-raster")]
ras,
[Description("application/rdf+xml")]
rdf,
[Description("image/x-rgb")]
rgb,
[Description("application/vnd.rn-realmedia")]
rm,
[Description("application/x-troff")]
roff,
[Description("text/rtf")]
rtf,
[Description("text/richtext")]
rtx,
[Description("text/sgml")]
sgm,
[Description("text/sgml")]
sgml,
[Description("application/x-sh")]
sh,
[Description("application/x-shar")]
shar,
[Description("model/mesh")]
silo,
[Description("application/x-stuffit")]
sit,
[Description("application/x-koan")]
skd,
[Description("application/x-koan")]
skm,
[Description("application/x-koan")]
skp,
[Description("application/x-koan")]
skt,
[Description("application/smil")]
smi,
[Description("application/smil")]
smil,
[Description("audio/basic")]
snd,
[Description("application/octet-stream")]
so,
[Description("application/x-futuresplash")]
spl,
[Description("application/x-wais-source")]
src,
[Description("application/x-sv4cpio")]
sv4cpio,
[Description("application/x-sv4crc")]
sv4crc,
[Description("image/svg+xml")]
svg,
[Description("application/x-shockwave-flash")]
swf,
[Description("application/x-troff")]
t,
[Description("application/x-tar")]
tar,
[Description("application/x-tcl")]
tcl,
[Description("application/x-tex")]
tex,
[Description("application/x-texinfo")]
texi,
[Description("application/x-texinfo")]
texinfo,
[Description("image/tiff")]
tif,
[Description("image/tiff")]
tiff,
[Description("application/x-troff")]
tr,
[Description("text/tab-separated-values")]
tsv,
[Description("text/plain")]
txt,
[Description("application/x-ustar")]
ustar,
[Description("application/x-cdlink")]
vcd,
[Description("model/vrml")]
vrml,
[Description("application/voicexml+xml")]
vxml,
[Description("audio/x-wav")]
wav,
[Description("image/vnd.wap.wbmp")]
wbmp,
[Description("application/vnd.wap.wbxml")]
wbmxl,
[Description("text/vnd.wap.wml")]
wml,
[Description("application/vnd.wap.wmlc")]
wmlc,
[Description("text/vnd.wap.wmlscript")]
wmls,
[Description("application/vnd.wap.wmlscriptc")]
wmlsc,
[Description("model/vrml")]
wrl,
[Description("image/x-xbitmap")]
xbm,
[Description("application/xhtml+xml")]
xht,
[Description("application/xhtml+xml")]
xhtml,
[Description("application/vnd.ms-excel")]
xls,
[Description("application/xml")]
xml,
[Description("image/x-xpixmap")]
xpm,
[Description("application/xml")]
xsl,
[Description("application/xslt+xml")]
xslt,
[Description("application/vnd.mozilla.xul+xml")]
xul,
[Description("image/x-xwindowdump")]
xwd,
[Description("chemical/x-xyz")]
xyz,
[Description("application/zip")]
zip
}