Twenty-three cases of basaloid squamous cell carcinoma (BSCC) and 23 stage-matched pairs of typical squamous cell carcinoma (SCC) of the oesophagus were investigated for molecular aberrations. Polymerase chain reaction (PCR) was used to detect loss of heterozygosity at the APC, RB, and MCC gene loci, while differential PCR was carried out to detect amplification of the CDK4 gene. In addition, the level of expression of the p53 and RB proteins in the tumour tissue was assessed by immunohistochemistry. Loss of heterozygosity (LOH) at the APC and MCC loci was about twice as common in BSCC as in SCC (40% vs. 21% and 33% vs. 12%, respectively), with co-existence of LOH at both loci occurring only in BSCC. LOH frequency at the RB gene locus was not remarkably different in either BSCC or SCC (20% vs. 24%, respectively). On immunohistochemistry, accumulation of p53 protein was slightly more frequent in BSCC than in SCC (61% vs. 52%), whereas the rate of loss of RB protein expression was about equal in both types of carcinoma (9% vs. 13% BSCC and SCC, respectively). There was no detectable amplification of the CDK4 gene in either type of tumour. Although the observed differences did not achieve statistical significance, this work has further highlighted possible differences between the molecular pathogenesis of BSCC and SCC.