We show that (i) a strong correlation exists between ROBO3 expression, AXL, and p-STAT3 in high-grade tumors with BL phenotype; (ii) ROBO3 controls STAT3 Y705 phosphorylation and IL-6–induced p-STAT3 activation and gene signatures in vitro and in vivo; and (iii) AXL tyrosine kinase is a potentially novel and critical player in the ROBO3/p-STAT3 signaling pathway that drives acquisition of the BL PDAC subtype. This evidence concerns the gene STAT3 and Burkitt lymphoma.