With the goal of finding serological markers to monitor patients with early as well as late-stage melanoma, we compared the levels of the cytoplasmic melanoma-associated antigens (CYT-MAA) and high-molecular-weightmelanomaassociated antigen (HMW-MAA) in the sera of melanoma patients and controls. Using double-sandwich ELISA, we measured levels of both antigens in 117 patients and in 62 age- and sex-matched controls. Patients were stratified into four risk group based on stage of the disease. Serum levels of both markers were significantly higher in melanoma patients than in controls. CYT-MAA was the more sensitive marker, with 61% of patients showing elevated levels regardless of the stage of disease. HMW-MAA was elevated in 29% . Elevated CYT-MAA was also significantly correlated with poorer clinical outcome. By multivariate analysis (adjusting for stage and age), patientswho had elevated CYT-MAA were 81% more likely to recur than patients with undetectable levels (hazard ratio = 1.81, 95% CI = [1.07, 3.06], p-value = 0.03). Elevated levels of HMW-MAA did not correlate with poor prognosis. These results suggest that both CYT-MAA and HMW-MAA are serum markers for residual melanoma in patients with resected disease. Furthermore, CYT-MAA appears to be a prognostic marker of clinical outcome in melanoma vaccine-treated patients. With the goal of finding serological markers to monitor patients with early- as well as late-stage melanoma, we compare the levels of the cytoplasmic melanoma-associated antigens (CYT-MAA) and high-molecular-weightmelanomaassociated antigen (HMW-MAA ) In the sera of melanoma patients and controls. Using double-sandwich ELISA, we measured levels of both antigens in 117 patients and in 62 age- and sex-matched controls. Patients were stratified into four risk group based on stage of the disease. Serum levels of both markers were significantly higher in melanoma patients than in controls. CYT-MAA was the more sensitive marker, with 61% of patients showing elevated levels regardless of stage of disease. HMW-MAA was elevated in 29% . Elevated CYT -MAA was also significantly corresponded with poorer clinical outcome. By multivariate analysis (adjusting for stage and age), patientswho had elevated CYT-MAA were 81% more likely to recur than patients with undetectable levels (hazard ratio = 1.81, 95% CI = [1.07, 3.06], p-value = 0.03). Elevated levels of HMW-MAA did not correlate with poor prognosis. These results suggest that both CYT-MAA and HMW-MAA are serum markers for residual Melanoma in patients with resected disease., CYT-MAA appears to be a prognostic marker of clinical outcome in melanoma vaccine-treated patients.