p27, a cyclin-dependent kinase inhibitor, suppresses proliferation of normal and neoplastic cells. Expression of p27 is correlated with survival in colon cancer. To some degree, right-sided colon cancers differ biologically and clinically from left-sided colon cancers. We analyzed 41 patients with right-sided colon cancers, including 18 cases with regional lymph node metastases and 23 cases with negative lymph nodes. Immunostaining for p27 was performed on histologic sections of primary cancers and scored. Correlation of p27 protein expression with histologic parameters was performed by t-test and multivariate analysis. Decreased p27 protein expression was associated with large tumor size. As percentages of positively stained tumor cells decreased from 70 to 29%, the mean tumor size increased from 1.9 to 7.3 cm. p27 protein expression significantly decreased in primary cancers with angiolymphatic invasion or with positive lymph nodes in comparison with those without angiolymphatic invasion (26 +/- 6 vs. 44 +/- 5%, P < 0.03) or with negative lymph nodes (23 +/- 4 vs. 47 +/- 6%, P < 0.003). p27 expression was not statistically different in terms of depth of tumor invasion (T1/T2 vs. T3/T4), tumor type or tumor differentiation. Multivariate analysis revealed that low p27 expression in primary cancers was correlated with lymph node metastases (P = 0.01). However, it did not correlate with any other histologic parameters. In summary, decreased p27 expression was associated with an increased likelihood of lymph node metastases in colon cancers, independent of depth of tumor invasion. This implies that p27 is a potentially important predictor for tumor metastasis and patient's prognosis in right-sided colon cancers.