Four tumour suppressor genes (Chk1, Chk2, Apaf1 and Rb1) in nine human malignant melanoma cell lines were screened for a loss of gene expression, point mutations and small deletions/insertions by cDNA-based DGGE/SCCP analysis. In two cell lines alterations of the investigated genes could be demonstrated. This result confirms our assumption of the participation of dysfunctional p53 inducer/effector genes in human melanoma aetiology. Furthermore, it points towards the probable principal role of diverse alternative p53-pathway disruption mechanisms in this highly therapy-resistant malignancy without affecting p53 itself. To our knowledge, this is the first CHK1/CHK2 mutation screening in human melanoma.