BACKGROUND: The prognostic value of morphometric nuclear features in Dukes' Stages B/C and D colorectal cancer (CRC) was assessed. PATIENTS AND METHODS: Primary tumours from 86 CRC patients were analysed, using an image overlay drawing system (Prodit Morphometry Program), for the following nuclear features: area, perimeter, diameter, form factor, roundness. RESULTS: The median nuclear area (NA) was 104.6 microm2 (range 57.2 - 237.2 microm2). The NA was larger in patients with lymph node metastasis (p < 0.02). Altogether, 43% of the patients showed clinical response to irinotecan-based chemotherapy. All six patients with complete response (CR) had a NA above the median (p < 0.03). The disease-specific survival of the patients with a NA above the median was significantly better than in patients with smaller NA (p < 0.02). CONCLUSION: Using the median NA as the cut-off value seems to effectively discriminate patients who are likely to respond to irinotecan-based chemotherapy (with improved prognosis) from those who are non-responsive and develop progressive disease.