To explore if ceramide accumulation in macrophages drives the TREM2 expression in the TME, we first conducted a thorough analysis of sphingolipids including the specific acyl-chain ceramides, sphingosine (SPH), Ceramide 1-phosphate (C1p) and sphingosine‐1‐phosphate (S1p) in the tumor tissue from MMTV mice and in the TAMs from PyMT NcDase−/− mice and EO771-bearing NcDasecKO mice. The gene discussed is TREM2; the disease is neoplasm.