Everybody gets lucky once in a while, but only endoscopically-guided tissue biopsies routinely provide useful results. Endoscopic mucosal biopsies, exploratory surgery, rigid proctoscopy. Endoscopy provides shallow biopsies that are difficult to interpret with respect to malignancy. Full-thickness samples usually are very limited in number and thus risk sampling error, and rigid scopes allow only distal colonic sampling. For suspected immune myopathy, take many small samples instead of one large piece.
Lesions often are very spotty and false negative results are frequent .
For suspected bone tumors, by far the biggest problem is inadequate depth of sample. These are terribly traumatic, bloody biopsies and it is tempting to stop before your core punch reaches the actual tumor which corresponds to the lytic area on the radiograph. Since the advent of ultrasound-guided liver core biopsies, the number of wedge biopsies obtained via exploratory surgery has fallen dramatically. Nonetheless, core biopsies cannot evaluate diseases characterized by macroscopic changes in hepatic architecture, and will miss diagnoses like cirrhosis, some cases of shunting, hepatoma and nodular hyperplasia, and focal inflammatory diseases. In my opinion, there is rarely indication for any type of kidney biopsy in dogs or cats.