We have previously reported complete responses and long-term survival following cisplatin-based combination chemotherapy in some patients with advanced poorly differentiated carcinomas of unknown primary site. In order to better define the clinical and pathologic characteristics of the chemotherapy-responsive subgroup, we have reviewed the case histories of our 32 patients who achieved complete response to combination chemotherapy. Initial light microscopic diagnoses were as follows: poorly differentiated carcinoma (23 patients), poorly differentiated adenocarcinoma (eight patients), or poorly differentiated large cell carcinoma (one patient). The median age was 37 years (range, 19-70); 25 of 32 patients were male. All patients had unresectable neoplasms at the time of diagnosis. Twenty-two patients had metastases at two or more locations. In 27 of 32 patients (84%), the predominant site of tumor involvement was either in the mediastinum, retroperitoneum, lymph nodes, or lungs. Six patients were assigned more specific diagnoses at some time during their clinical course on the basis of further pathologic evaluation, additional biopsy material, or autopsy: germinal tumors, two patients; adenocarcinoma of the lung, one patient; carcinoid tumor of the lung, one patient; and malignant melanoma, two patients. Eighteen patients (56%) remain continuously disease free at a median of 77 months following diagnosis and are considered unlikely to recur. All patients with poorly differentiated carcinomas and tumor location in the mediastinum, retroperitoneum, lungs, or lymph nodes should be considered for treatment with intensive cisplatin-containing combination chemotherapy, since some of these patients have potentially curable malignancies.