Neuroblastoma is an embryonal tumor of neural crest origin noted for its heterogeneity at the clinical, histologic, and molecular levels. The deleted in colorectal cancer (DCC) protein is an adhesion family molecule of unequivocal importance in neural development that has also been implicated in several malignancies, including neuroblastoma, through its apparent loss of function. Immunohistochemical assessment of the DCC protein was performed on a group of 49 neuroblastoma specimens and examined in relation to important clinical, histologic, and molecular parameters. DCC expression was significantly associated with neuroblastoma dissemination as primary tumors from Stage 1 to 3 patients (15/20, 75%) more frequently exhibited the DCC protein than those from Stage 4 patients (5/13, 38%; p = 0.0415). Primary tumors were more frequently DCC-positive (20/33, 61%) as compared with metastatic deposits (3/16, 19%; p = 0.0063), and a single case of a paired primary and metastatic deposit demonstrated the apparent loss of DCC gene expression with tumor progression. The remaining five paired specimens were DCC-negative in both the primary tumor and metastatic deposit. No significant association was appreciated between DCC expression and patient age, the Shimada histologic classification, or N-Myc amplification. These results provide evidence that DCC expression may be lost in the course of metastatic spread in a subset of neuroblastomas. Moreover, DCC function is implicated in neuroblastoma dissemination in a manner independent of N-Myc.