Cell adhesion molecules influence the progression of some human pathologies. The aim of our study was to investigate the possible relationship between L-selectin Pro213Ser (P213S) gene polymorphism and four common diseases in Romanian population (colorectal cancer, chronic periodontitis, type 2 diabetes, metabolic syndrome). Blood samples were obtained from 770 subjects represented by patients and controls matched by sex and age. Genomic DNA was extracted from peripheral blood leucocytes using commercial kits and the P213S L-selectin polymorphism was genotyped by PCR-RFLP. Statistical analysis was performed using the StatsDirect software. For colorectal cancer (CRC), the study revealed a high frequency of the PP genotype in the control group compared with CRC patients group (70% vs. 59.4%). The S allele may represent a risk factor (OR= 1.59, p= 0.04) whereas the PP genotype may be protective (OR= 0.62, p= 0.04) for CRC. We find no other significant association between P213S and investigated diseases. These findings suggest that the P213S L-selectin gene polymorphism may contribute to the susceptibility to colorectal cancer in Romanian patients.