BACKGROUND: Metastatic cancer of unknown primary site occupies 0.5-10% of all diagnosed cancer patients and includes various tumors with diverse responses to systemic chemotherapy. Adenocarcinoma of unknown primary site (ACUPS), the most common subtype, has no standard treatment, rarely responds to conventional treatment and has a poor survival rate. METHODS: The retrospective study was performed to investigate the clinical characteristics and the treatment outcomes of ACUPS. RESULTS: Eighty-one patients with ACUPS diagnosed at Samsung Medical Center from May 1995 to July 1999 were included. The median age was 58 years (range, 29-77). The common sites of metastases were the lymph node, liver, lung and bone in order. In 49 of 81 patients (60.5%), the dominant tumor location was below the diaphragm. The majority of patients (76 of 81) were initially treated with systemic chemotherapy including cisplatin. Responses were evaluable in 70 of 76. Eighteen of 70 patients (25.7%) responded to chemotherapy and complete remission was observed in 6 patients. The overall median survival of 81 patients was 5.6 months. The median survival of the responding patients was 18.3 months but the median survival of the nonresponding patients was 4.6 months (p < 0.01). In univariate and multivariate analysis, age, performance status and response to initial chemotherapy were significant prognostic factors for overall survival. CONCLUSION: We observed poor response to the treatment and survival rate in ACUPS, but complete remission and long-term survival were observed in a small number of patients.