Despite an apparently curative resection more than 50% of patients with non-small cell carcinomas (NSCLC) will relapse after surgery. Therefore, it has to be assumed that in a substantial number of patients a tumor cell dissemination has occurred already at the time of surgery. In a prospective study we analyzed the extend of an early regional tumor cell dissemination into lymph nodes and/or a systemic tumor cell dissemination into the bone marrow in 91 patients with completely resected NSCLC by using sensitive immunocytochemical techniques. A tumor cell dissemination limited to the regional lymph nodes was detected in 14 (15.4%) patients. A systemic dissemination of tumor cells into the bone marrow alone in 10 (11.1%) patients. In 6 patients (6.6%) both body compartments were involved by immunocytochemistry. The detection of a nodal and a systemic tumor cell dissemination was associated with a significantly shortened disease free survival (p = 0.002 and p = 0.05, respectively). A Cox regression analysis demonstrated that the detection of tumor cells by immunocytochemistry is an independent prognostic factor (p = 0.018). In conclusion the detection of disseminated tumor cells by immunocytochemistry is an useful prognostic parameter, which underlines the requirement of a multimodal therapeutic strategy in these patients.