There is much interest in use of identity-by-descent (IBD) methods to map genes, both in Mendelian and in complex disorders. Homozygosity mapping provides a rapid means of mapping autosomal recessive genes in consanguineous families by identifying chromosomal regions that show homozygous IBD segments in pooled samples. In this report, we point out some potential pitfalls that arose during the course of homozygosity mapping of the enhanced S-cone syndrome gene, resulting from (1) unexpected allelic heterogeneity, so that the region containing the disease locus was missed as a result of pooling; (2) identification of a homozygous IBD region unrelated to the disease locus; and (3) the potential for inflation of LOD scores as a result of underestimation of the extent of inbreeding, which Broman and Weber suggest may be quite common.