Willemite is a common mineral mainly occurring in the so-called “hypogene” nonsulfide Zn-Pb mineralizations, deposited from what have been interpreted as high temperature hydrothermal or metamorphic fluids. The literature is currently lacking a comprehensive compilation of geochemical data on willemite so the aim of this study was to elucidate specific geochemical signatures for willemites of contrasting genesis. For this work, we analyzed a range of specimens from the Mineralogy Collection of the Natural History Museum in London. The specimens are from several deposit-types: 1.Stratiform hypogene deposits: Franklin and Sterling Hill (USA);2.Structurally-controlled hypogene deposits: Star Zinc, Excelsior, Surprise (Lusaka area, Zambia), Kabwe (Zambia), Berg Aukas and Tsumeb (Namibia);3.Supposedly supergene deposits: Mumbwa area (Zambia), and Altenberg-Vieille Montagne (Belgium).Textures and structures of the willemite-bearing specimens were initially investigated by scanning electron microscope energy dispersive analysis (SEM-EDS). Trace element concentrations were later measured in situ on selected willemite crystals by laser ablation (LA)-ICP-MS. Statistical analyses (principal component analysis-PCA, multivariate analysis of variance, post hoc Tukey HSD test), conducted on the data obtained by LA-ICP-MS, showed that significant differences exist between willemites derived from the various deposit types studied. High-T, stratiform willemite samples contain significant amounts of Mn and Mg, and are statistically different from all the other analyzed specimens. Structurally-controlled hypogene willemites, characterized by lower Mn and Mg concentrations, and by higher Pb, Cu, As, B, Ge contents, are statistically inhomogeneous, both at the district and at the deposit scale. High-T willemite from the Lusaka area contains more Mn than the low-T hydrothermal deposits, with the latter showing higher concentrations of other elements (e.g. Pb, Cu, Ge). Among the willemite generations associated with the supposedly supergene mineralization, only the Mumbwa willemites form a cluster that is significantly displaced from the other deposits. The δ18O isotopic compositions match the mentioned trace element distribution: willemites with similar origin are characterized by similar oxygen isotopic ratios. On the basis of the present work, willemite-types can be distinguished as follows:•High-T willemites are characterized by high Mn + Mg concentrations (between 100 ppm to unit wt%) and by low, positive δ18O compositions (around 3 to 5‰ V-SMOW);•Low-T hydrothermal willemites show Mn + Mg concentrations below 50 ppm and are associated with high Pb + Cu + As + Ge concentrations (above 100 ppm). They also have high, positive δ18O compositions (between 9 and 15‰ V-SMOW);•Willemites derived from (either cold or warm) meteoric fluids have generally low concentrations of the above elements and negative δ18O compositions (−3 and −9‰ V-SMOW). The supposedly supergene Altenberg-Vieille Montaigne willemite, having low Mn + Mg and high Pb + Ge + As concentrations, and showing δ18O compositions between 11 and 12.5‰, likely formed from low-T hydrothermal fluids.