To date, several tumor-suppressor genes responsible for the tumorigenesis of colorectal cancer have been identified. However, studies of loss of heterozygosity (LOH) have suggested several chromosomal regions which may contain additional tumor-suppressor genes for colorectal cancer. To determine the extent and variation of allelic loss on 22q, on which LOH has been frequently observed, a total of 68 sporadic colorectal cancers was examined for LOH on the chromosome arm by means of 16 polymorphic DNA markers. LOH was observed in 28 tumors (41%), of which 9 showed LOH at all informative loci. The remaining 19 tumors showed variable patterns of partial loss on 22q, delimiting the smallest region of overlap (SRO) between D22S90 and D22S94. Moreover, LOH within the SRO correlated with a progression in terms of Dukes' stages. These results suggest that an additional tumor-suppressor gene for colorectal cancer may exist on 22q distally to the NF2 locus and that inactivation of the gene may possibly play a role in the progression or metastasis of colorectal cancers.