In this study, an acquired pigmentation in Nero Siciliano pigs is reported and evaluated by a multidisciplinary approach to support the hypothesis it is caused by an ingested material. A total of 18 pigs were studied. Fourteen conventionally slaughtered animals showed black discoloration of lymph nodes. The lymph nodes were normal in size and shape but showed diffuse black discoloration of the cortex and medulla. Melanosis of fat was observed in 2 animals and was limited to the back. Histochemical tests performed on tissues enabled identification and differentiation of the pigment. Immunohistochemical staining for macrophage markers showed macrophages containing a variable amount of melanin-like granules. Stains for human melanoma, as well as S-100 protein, did not show any reaction. Histochemical methods for tyrosinase showed colorimetric patterns that confirmed the presence of the enzyme in acorns. The activity was mostly latent. A high tannin content was demonstrated, reaching about 76% of the total phenolic compounds. Our data, and the well-known steps on melanin formation, permit us to hypothesize that swine tyrosinase could act on phenolic substances found in acorns. Tyrosinase activation could take place in genetically predisposed swine after acorns are eaten, and this event could increase the biosynthesis and the anomalous storage of melanin.