To examine the malignant potential of submucosal invasive colorectal carcinoma, the relationship between proliferating cell nuclear antigen (PCNA) expression and clinicopathologic risk factors for lymph node metastasis was studied in 149 patients with submucosal invasive colorectal carcinoma. The depth of submucosal invasion was classified as scanty or massive. Histologic subclassification at the submucosal deepest invasive portion was done as follows: well differentiated (W), moderately well differentiated (Mw), moderately poorly differentiated (Mp) or poorly differentiated (Por). Tumor growth was divided into polypoid growth and nonpolypoid growth. The PCNA expression (labeling index, LI) was examined at the submucosal deepest invasive portion. The PCNA-LI of tumors showing lymph node metastasis (mean, 56.5 +/- 19.0%) was significantly higher than that of tumors without lymph node metastasis (mean, 41.5 +/- 19.3%; p < 0.01). The PCNA-LI of Mp tumors (mean, 57.7 +/- 16.5%) was significantly higher than that of W (mean, 38.5 +/- 19.0%; p < 0.05) and Mw (mean, 43.7 +/- 19.1%; p < 0.05) tumors. The PCNA-LI of tumors without adenomatous features (mean, 47.9 +/- 20.5%) was significantly higher than that of tumors with such features (mean, 37.1 +/- 17.1%; p < 0.05). The PCNA-LI was not correlated with other risk factors for lymph node metastasis, such as lymphatic invasion, depth of submucosal invasion, macroscopic type, and growth pattern. These results indicate that the PCNA-LI may be useful marker for predicting the potential metastases to lymph nodes in submucosal invasive colorectal carcinoma, while the proliferative activity of cancer cells correlates with the degree of the differentiation in the area of deepest invasion.