Serum tumor markers are useful to evaluate a cancer's response to treatment, for early detection of cancer relapse, and, in some cases, to diagnose malignancy. In this paper, we present two patients with significantly elevated serum tumor markers without evidence of malignant disease. An 18-year-old patient suffering from autoimmune hepatitis had markedly increased alpha-fetoprotein (aFP) levels (2,002 μg/L; normal <10 ug/L). Extensive imaging showed no signs of hepatocellular carcinoma or other cancer, and treatment with Prednisone led to rapid normalization of both liver enzymes and aFP. The second patient, a 60-year-old female with painless jaundice due to biliary stone disease, had very high serum levels of CA19-9 (18,000 kU/L, normal <27 kU/L). Liver biochemistry and serum CA19-9 concentration decreased to almost normal values (45 kU/L) after biliary stenting. These cases demonstrate that serum tumor markers can be elevated in benign disease and are therefore not appropriate to diagnose cancer.