BTK and neoplasm: Antimicrobial peptides (AMPs), evolutionarily conserved effectors of innate immunity, possess selective cytotoxicity against malignant cells by exploiting tumor-specific membrane alterations.<h4>Methods</h4>Peptides were synthesized and tested for their anti-proliferative activity in MZL cell lines.<h4>Results</h4>We evaluated the antitumor activity of seven natural AMPs, including Antarctic fish-derived trematocines and chionodracine variants, and amphibian temporins, against MZL cell lines (VL51, Karpas1718) and derivatives resistant to BTK, PI3Kδ, or PI3Kα/δ inhibitors.