BACKGROUND Urinary levels of tissue polypeptide specific antigen (TPS, cytokeratin-18) have been proposed as a marker of urothelial malignancies. Previous studies have shown that serum TPS levels are elevated in alcoholics. This study was designed to determine whether alcoholics had elevated urinary TPS levels as well. METHODS Serum and urinary TPS levels were determined in 24 alcoholics and 15 healthy controls by means of a commercial chemiluminiscent immunoassay. RESULTS Serum TPS levels were higher in alcoholics than in controls (median 332 U/L, range 51-21241 U/L versus median 17 U/L, range 15-65 U/L, respectively, p<0.001). Urinary TPS levels were also higher in alcoholics than in controls (median 244 U/L, range 22-1267 U/L versus median 66.5 U/L, range 15-600 U/L, respectively, p=0.001). Urinary TPS levels were correlated with serum TPS levels in alcoholics. CONCLUSIONS Urinary TPS levels are elevated in alcoholics. Consequently, the specificity of urinary TPS as a tumor marker may be limited in alcoholics.