The CHEK2*I157T missense mutation, reported in ethnically diverse, high-risk families, moderately increases breast and colon cancer risk. The present study assessed whether this mutation represents a founder mutation. Participants identified in high risk clinics or from consecutive cancer patients in Israel, Poland, Latvia, and Finland, were either carriers of the CHEK2*I157T mutation or non-carrier family members. Multi-locus genotyping employed two intragenic markers and five CHEK2 gene flanking markers, spanning about 645 kb. Haplotyping was done when families were available for phasing. Overall, 101 individuals (83 I157T*CHEK2 mutation carriers) were genotyped: 16 Finnish individuals from 11 families (14 mutation carriers, two non-carrier family members), 50 Polish individuals (20 families) (35 carriers, 15 non-carriers), 28 unrelated Latvian mutation carriers, and seven Israeli participants (two families) (six mutation carriers, one non-carrier). Overall 36/83 mutation carriers (43%) were diagnosed with breast cancer, 15/83 (18%)-colon cancer, three-ovarian cancer, one-thyroid cancer, and the rest (n = 28) were asymptomatic. A common core haplotype was detected in all I157T*CHEK2 mutation carriers of Israeli, Polish, and Finnish origin between markers D22S275-D22S689 (approximately 258 kb), with a different allele pattern in Latvians. In conclusion, CHEK2*I157T missense mutation is a founder mutation in ethnically diverse populations, but may also be a mutational hotspot.