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Background. The occurrence of independent synchronous esophageal carcinoma in patients with grossly invasive esophageal cancer (GEC) is well known. Although multiple primary carcinoma of the esophagus is not uncommon, the exact prevalence is controversial, and its clinicopathologic features remain relatively unknown. Methods. Fifty-four patients with squamous cell GEC who underwent transthoracic esophagectomy with systematic lymphadenectomy between 1987 and 1991 at the Institute for Digestive Diseases, Belgrade University Clinical Center, were included in the study. Results. Detailed histopathologic examination of the esophagus resected for squamous cell carcinoma was performed in 54 patients and revealed 17 patients (31%) with associated cancer independent of the main tumor. The second lesion was significantly less invasive than the main tumor. There was no significant difference (P = 0.06) in sex, age, main tumor site, tumor differentiation, tumor diameter, lymph node involvement, or tumor stage between patients with multiple cancer and patients with solitary cancer, but there was a significant difference in the depth of invasion (P < 0.01). The tumor stage in patients with multiple cancer was determined by the main tumor stage and was not influenced by the associated lesion. The prevalence of multiple primary cancer of the esophagus is lower in other reports than in this series. Conclusions. The patients in this study had significantly more invasive main tumors. It seems likely that a higher prevalence of multiple cancer may be expected in patients with advanced main tumor penetration. These results support the concept that the entire esophagus may be considered as one entity of field cancerogenesis. Cancer 1994; 73:2687-90.