dlk encodes a transmembrane protein member of the EGF-like family of homeotic proteins. dlk is expressed in the same type of neuroendocrine tissues and tumors as pG2, a gene cloned because of its differential expression in human pheochromocytomas versus neuroblastomas. Human dlk and pG2 cDNAs are around 98% similar in sequence, but the predicted proteins encoded by those genes are apparently unrelated. This fact suggested the existence of polymorphic variants of the same gene. We have sequenced again several pG2 and dlk clones in parallel. We identified a pG2 cDNA species corresponding to an alternatively spliced dlk mRNA, as well as several other variant forms of dlk mRNA. One of the pG2 clones resulted to be identical to human dlk and encode the same EGF-like protein. Pref-1, a cDNA isolated from 3T3-L1 fibroblasts, encodes a putative protein possessing an extracellular EGF-like domain similar to dlk, but a different intracellular region. Analysis of sequence data from different clones obtained in our laboratory confirmed some of the differences between dlk and Pref-1. However, the putative difference in the intracellular regions of dlk and Pref-1 was due to sequence artifacts. These data suggest that dlk, pG2 and Pref-1 are variant products of the same gene.