In summary, we first reported the existence of lnc-HOXB8-1:2 in neuroendocrine differentiated CRC-derived exosomes, and lnc-HOXB8-1:2 acted as a ceRNA competitively binding hsa-miR-6825-5p to regulate the lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis, leading to the infiltration and M2 polarization of TAMs, which serves an oncogenic role in CRC progression. The gene discussed is HOXB8; the disease is colorectal carcinoma.