NF-kappaB is a transcription factor believed to mediate a cellular survival response following the apoptotic stimulus TNF-alpha. To clarify the role of NF-kappaB in colorectal cancer, we investigated the relationship of NF-kappaB expression by immunohistochemistry with clinicopathological variables, and other factors including apoptotic index, bcl-2 expression, p53 and K-ras mutations in 138 colorectal adenocarcinomas. Eighty-seven (63%) tumours showed cytoplasmic and 51 (37%) nuclear NF-kappaB expression. Nuclear NF-kappaB was correlated with mucinous carcinomas (p=0.006) and was more apparent in the invasive margin of some tumours. A trend was seen between nuclear NF-kappaB expression and K-ras mutation (p=0.15). However, NF-kappaB was not correlated with gender, age, tumour location, Dukes' stage, survival, apoptotic index, bcl-2 expression and p53 mutations. Conclusively, NF-kappaB might be activated in more aggressive colorectal tumour cells, since both tumour cells in the invasive margin and the mucinous tumour cells could represent more aggressive tumour cells.