The role of p53 and bcl-2 apoptosis related proteins in the pathogenesis of endometrial cancer remains unclear. We immunohistochemically examined 133 surgically removed tumour specimens from patients with stage I endometrial cancer for p53 oncoprotein nuclear expression and bcl-2 cytoplasmic reactivity. 114/133 (86%) cases were of the endometrioid histological sub-type. A cut-off point of 10% of cells with strong reactivity was used for positivity. Positive p53 expression was observed in 12/133 (9%) and positive bcl-2 in 40/133 (30%) cases. p53 expression was not related to bcl-2 expression. No association of p53 and bcl-2 with depth of myometrial invasion, vascular invasion or histological grade was observed. However, continuous variable analysis revealed a trend of low grade cases to have a higher percentage of bcl-2 positive cells (16.3 + 27% vs. 7.8 + 16%; p = 0.09, unpaired two tailed t-test). Interestingly, a statistically significant association of p53 positivity with age was also observed (p = 0.03). A strong association of high grade with depth of myometrial invasion (p = 0.006) and vascular invasion (p = 0.0001) was also noticed. In addition, the presence of adenomyosis was also associated with low grade (p = 0.01) and absence of vascular invasion (p = 0.02). We conclude that although loss of bcl-2 protein expression and p53 mutant protein nuclear accumulation are early events in the endometrial cancer progression, histological grade and vascular invasion remain the most important factors defining local invasive behaviour of endometrial cancer.