Lymphoma is a relatively prevalent cancer in dogs accounting for as much as 25% of all canine cancer diagnoses. There is also strong evidence for breed-dependent predisposition to lymphoma, indicating that dogs may provide a very useful model for studying the genetic component of this complex disease to complement the knowledge gained from human studies. There have been a number of studies that have identified the lymphoma risk of individual breeds, and a number of breeds have been consistently recognised as having a relatively increased or decreased risk. Using the recently developed sensitive method of composite selection signal (CSS) analysis and high resolution SNP array genotyping data, the aim of the present study was to identify selection signatures in the Mastiff-like breeds that correspond to lymphoma susceptibility. The CSS approach was utilised to identify selection signals in the highly susceptible European Mastiff group versus other breeds. Using the top 0.001 fraction (0.1%) of CSS values, a total of 10 significant regions containing 492 genes were identified as being positively selected in the European Mastiff-like dogs. When all comparisons were considered and the significant regions were merged, the number of candidates was reduced to 205 genes from three significant regions located on chromosomes CFA1, CFA9 and CFA26. The region located on chromosome 26 (CFA26:5.92-8.72 Mb) harbouring 73 SNPs was identified in each pairwise comparison. Our findings provide supporting evidence for previously described selective sweep regions in brachycephalic dogs. The CFA 26 region has been strongly associated with the brachycephalic breeds, which are defined by strong selection based on a flat-faced skull shape. This artificial selection process may have inadvertently selected for haplotypes or specific gene variants that contribute to an increased prevalence of lymphoma in these breeds. However, this region may have been transmitted directly from Bulldogs.