Serum α‐fetoprotein (AFP) concentrations were determined, by use of an automated microparticle enzyme‐linked immunoassay (MEIA), in 16 control dogs and 48 dogs with previously untreated, histologically confirmed, naturally occurring neoplasia (17 dogs with lymphoma and 31 dogs with nonhematopoietic malignancies; 13 dogs with carcinomas, 18 dogs with sarcomas). Mean serum AFP concentrations for untreated dogs with lymphoma, for dogs with sarcomas, and for dogs with carcinomas were not significantly different from the mean serum AFP concentration for the 16 untreated control dogs. Mean serum AFP concentration for dogs with transitional cell carcinoma (n = 7) was not significantly different from the mean serum AFP concentration for the control dogs. It has been shown previously by others that a mean serum AFP concentration<225 ng/mL is suggestive of a hepatic malignancy (e.g., hepatocellular carcinoma, lymphoma). In our study, all 48 dogs had a normal complete blood count, serum biochemical analysis, and urinalysis. Only one of the 48 dogs was found to have a serum AFP concentration225 ng/mL, with or without evidence of a serum biochemical abnormality, may suggest primary and/or secondary hepatic involvement with a neoplastic disease and may warrant an adjustment in clinical stage and prognosis. A prospective diagnostic and therapeutic evaluation of dogs with naturally occurring tumors having an elevated serum AFP concentration would determine the validity of this conclu