The aim of the study was to analyze the relation between tumor volume (V(path)), tumor marker index (TMI) and prognosis in 261 completely resected (R0) stages I and II non-small cell lung cancer (NSCLC) patients by univariate and multivariate analyses. V(path) was calculated as an ellipsoid body. TMI represents the geometric mean of normalized CYFRA 21-1 and CEA values. Patients with a V(path)< or =13.7cm(3) had a significantly better 5-year-survival rate than patients with a V(path)>13.7cm(3) (78.1% vs. 47.9%; p<0.001). Patients with a TMI< or=0.54 had a 5-year-survival rate of 79.1% compared to only 47.2% in patients with a TMI>0.54 (p<0.001). Besides age (>70 years), performance status and gender, both V(path) (>13.7 cm(3)) and TMI (>0.54) bore significance in the multivariate Cox model with a hazard ratio (HR) of 1.9 (95% CI: 1.1-3.3, p=0.016) and 2.3 (95% CI: 1.3-4.2, p=0.006), respectively. Based on a combination of V(path) and TMI, a low risk group (17% of the patients) with both parameters in the normal range could be identified. Patients with elevated V(path) or TMI (31%) had an intermediate HR of 3.4 (95% CI: 1.3-9.2). When both factors were elevated (52% of patients) the HR increased to 5.95 (95% CI: 2.4-14.9). The elevation of V(path) and TMI was found in 46.2% of stage I and in 59.1% of stage II. The 5-year-survival rates were found to be 89.1, 62.2 and 43.0%, respectively. In conclusion, elevated levels of TMI and V(path) have a strong negative prognostic impact on survival in operated early stage of NSCLC. These patients might be considered for adjuvant chemotherapy.