The PDGFB gene (platelet derived growth factor receptor beta) belongs to the platelet-derived growth factor family and encodes a protein which acts as a receptor tyrosine kinase. The most frequent translocation involving the PDGFB gene is t(17;22)(q21.3;q13.1) juxtaposing the PDGFB gene next to the COL1A1 gene in 17q22. Reciprocal translocations involving t(17;22)(q21.3;q13.1) are characteristic for dermatofibrosarcoma protuberans (DFSP) patients. DFSP is a highly recurrent, infiltrative skin tumor of intermediate malignancy. The rearrangements are cytogenetically characterized by the presence of supernumerary ring chromosomes containing low-level amplified sequences from chromosomes 17q22-qter and 22q10-q13.1, or unbalanced derivatives of the t(17;22) (q21.3;q13.1) translocation. The rearrangement results in a COL1A1-PDGFB fusion protein which is post-transcriptionally processed to a functional platelet-derived growth factor beta chain (PDGFB) protein. The importance of accurately diagnosing DFSP lies in its intermediate malignant nature and the availability of a therapy with significant anti-neoplastic activity but relatively minor adverse effects for cases not amenable to surgical excision.