The current strategy for clinical use of CDK4i/6i in patients with advanced ALM rests upon the genetic status of CDK pathway nodes, in part due to recent evidence that Cdk4 and/or P16INK4a copy number status may be of prognostic significance for ALM patients [7]; stemming from this study, only patients with CDK4 gain, CCND1 gain and/or CDKN2A loss were eligible for treatment with palbociclib [8]. Here, CDK4 is linked to acral lentiginous melanoma.