The presence of lymphocytic infiltrates within primary cutaneous malignant melanoma (CMM), documented spontaneous tumour regression and genetic linkage with chromosome six in familial cases all suggest that immunogenetic factors may modulate disease progression. An association has been suggested between HLA DQB1*0301 and CMM in US patients but no such investigation has been performed in the UK population. Polymerase chain reaction-based HLA class II DRB1, DQA1 and DQB1 typing of 99 UK-based CMM patients was performed using DNA extracted from archival formalin-fixed and paraffin wax-embedded surgical biopsies, enabling retrospective access to clinical follow-up data. An increase in frequency of the HLA DQB1*0303 genotype among CMM patients was identified compared to control subjects (19.2% vs 5.8%; Pc=0.003; RR=3.9) while HLA DQB1*0301 was associated with more advanced and therefore poorer prognosis primary tumours (e.g. HLA DQB1*0301 allele frequency: 20.1% vertical growth phase vs 4.0% horizontal growth phase; Pc=0.03; RR=6.1). These findings suggest that the HLA DQB1 locus, and in particular the HLA DQB1*0303 and *0301 alleles, may play an important role in determining the risk of development and the prognosis of CMM within the UK population.