Recognizing the fact that both the stimulatory and inhibitory domains coexist in the Plexin-B1 cytoplasmic domain, we speculate that "intra-molecular" preferential Plexin-B1 signaling pathways in cancers could constitute a sound explanation to reconcile these conflicting clinical results of Plexin-B1 in tumor progression. The gene discussed is PLXNB1; the disease is cancer.