The serum fraction obtained by ammonium sulfate fractionation between 50 and 60% saturation was utilized for studies of serum tyrosinase. Normal individuals showed lowest serum tyrosinase activity, and patients with melanoma and breast carcinoma had the highest serum tyrosinase activities. Individuals with six other malignant diseases showed intermediate serum tyrosinase activities. The electrophoretic patterns of normal serum tyrosinase revealed no clear peak, whereas peaks were demonstrable in sera derived from all individuals with malignant disease. The tyrosinase isozyme released by lipase digestion appears associated with the globulin fraction of the serum. The observed differences in serum tyrosinase activity suggest that the development of a reliable diagnostic assay may be possible.