We found that certain aggressive and metastatic nodular-like melanomas with low NAEs but high 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG), 2-AG, and ARA levels can progress without MAGL and upregulate CES1 to drive the hydrolysis of 2-AG, 2-oleoylglycerol (2-OG), and other glycerol esters (Fig. 1). Here, CES1 is linked to melanoma.