A carcinoma of unknown primary (CUP) is a histologically confirmed metastatic cancer without a definitive primary site after performing a detailed medical examination. The purpose of the study was to classify unfavorable CUPs into more reliable disease entities, which reflect the clinical course. We reviewed the medical records of patients diagnosed with a CUP between January 1995 and March 2008. Patients were classified into a conventional favorable-risk group and a newly proposed unfavorable-risk group according to the clinicopathologic features. Five hundred eighty-six patients were diagnosed with CUPs. Fifty-six (9.6%) patients were classified in the conventional favorable-risk group, and 486 (82.9%) patients were classified in the unfavorable-risk group. We further classified the 486 patients into six subgroups with an unfavorable risk, while excluding 29 patients (5.0%) who were not classifiable. The overall survival of the conventional favorable-risk group was 47.0 months (95% CI, 11.1~82.9 months), which was significantly longer than that of any subgroup of the newly proposed unfavorable-risk group (P < 0.001). Patients with squamous cell carcinoma in the abdominopelvic cavity showed similar overall survival with unfavorable-risk group (P = 0.484). Women with non-papillary malignant ascites had a survival in between the favorable and unfavorable groups (P < 0.001). The newly proposed unfavorable-risk group may assist in classifying CUP patients with an unfavorable risk in a clinically more meaningful way. Squamous cell carcinoma in the abdominopelvic cavity should be considered in the unfavorable-risk group and women with non-papillary malignant ascites in an intermediate-risk group. Further studies with molecular profiling would help in classifying and treating patients with CUPs and an unfavorable risk.