This study examined p53 expression immunocytochemically in 40 lingual squamous cell carcinomas from Dutch patients with known histories of smoking and/or drinking alcohol. 30% of neoplasms showed positive p53 reactivity, suggesting increased levels of p53 protein. No alcohol or tobacco risk factors were evident in 33.3% (4/12) of p53-positive neoplasms whereas only 7.1% (2/28) of p53-negative neoplasms showed an absence of these risk factors. 25% (3/12) of p53-positive neoplasms and 71.4% (20/28) of p53-negative neoplasms were found in patients who had been exposed to both alcohol and tobacco. A similar negative association with p53 reactivity was also found when either tobacco or alcohol were used in isolation. The results contrast with previous observations in head/neck and oral carcinomas and indicate that the association of alcohol/tobacco and p53 expression remains open to question.