The clinical behavior and response to therapy of rare histologic variants of esophageal carcinoma are unclear. To evaluate the results of therapy in this group the records of 29 patients treated between 1949 and 1991 with primary rare histologic variants of esophageal carcinoma were retrospectively reviewed. This group represented 1.2% of 2454 cases of esophageal carcinoma treated between 1949 and 1991 and included mucoepidermoid (n = 14), small-cell (n = 12), adenoid cystic (n = 2), and carcinosarcoma (n = 1) carcinomas. Treatment for localized disease consisted of esophagectomy in five of seven patients with mucoepidermoid carcinoma, two of six patients with small-cell carcinoma, two of two patients with adenoid cystic carcinoma, and one of one patient with carcinosarcoma. Patients with stage IV mucoepidermoid carcinoma were treated predominately with radiation therapy (5/7). The majority of small cell carcinomas were treated with multiagent chemotherapy (10/12). The 1- and 3-year disease-specific survivals were 54% and 9% for mucoepidermoid carcinoma (median survival, 5 months) and 16% and 0% for small-cell carcinoma (median survival, 7 months), respectively. Patients with stage III mucoepidermoid carcinoma (median survival, 20.5 months) compared with those with stage III small-cell carcinoma (median survival, 6.2 months) had a significantly longer duration of survival (p < 0.05). Distant disease was present in 86% of patients in whom recurrence developed after esophagectomy Esophagectomy is standard therapy for localized carcinomas of the esophagus. Small-cell carcinoma appears to be a more aggressive variant of carcinoma and is most commonly treated with chemotherapy.