Human heart, lung and kidney express a 6 kb mRNA encoding Ror1, a member of the receptor tyrosine kinase (RTK) family with as yet unknown ligand specificity. We used a Ror1 cDNA probe to screen a cDNA library prepared from the human neuronogenic teratocarcinoma line, NTera2, and cloned a 2373 nucleotide transcript. This transcript contains an open reading frame that encodes a 388 amino acid protein identical with the cytosolic, C-terminal region of ror1 but lacking the ror1 transmembrane and entire extracellular domains. Northern blots demonstrate that mRNA encoding this truncated Ror1 ('t-Rorl') is abundantly expressed in fetal and adult human CNS, in human leukemia, lymphoma cell lines, and in a variety of human cancers derived from neuroectoderm. While previous studies have documented alternative splicing patterns within 5' and 3' regions of mRNAs encoding various RTKs altering their ligand binding specificity or their intracellular signaling, the present report is the first to demonstrate tissue-specific alternative mRNA splicing causing loss of the entire extracellular and transmembrane regions of an RTK.