Little is known about the Bcl-2 family members in mesothelioma. These proteins are involved in the control of apoptosis, carrying out both pro- and anti- apoptotic functions. Immunohistochemistry was used to examine the expression of p53 and Bcl-2 family members in 54 archival mesothelioma samples (39 epithelial, 15 sarcomatoid tumours). Overexpression of p53 was observed in 81% (44/54). For anti-apoptotic proteins, overexpression was recorded as follows: Bcl-2 40% (22/54), Bcl-XL 24% (13/54), Mcl-1 92% (50/54). For pro-apoptotic proteins, loss of expression was recorded as follows: Bad 25% (14/54), Bak 24% (13/54), Bax 42% (23/54), Bid 37% (20/54), Bim 18% (10/54). Statistically significant differences between epithelial and sarcomatoid tumours were observed for Bid (p < 0.001), Bad (p = 0.012) and Bcl-XL (p = 0.03). Significant differences in abnormal expression of apoptosis proteins were found between epithelial and sarcomatoid subtypes but histological subtype was the only factor with significant association to patient prognosis.