In this first report of alternative TrkA mRNA splicing in CMMs and TrkA splice variant behaviour in BRAF(V600E)-mutated A375 melanoma cells, we demonstrate a possible causal relationship between reductive stress, UPR activation, alternative TrkA splicing and TrkAIII expression and activation, consistent with a targetable, pro-survival, oncogenic role for TrkAIII in metastatic CMM progression. Here, NTRK1 is linked to melanoma.