We investigated the role of the passive volcanic plume of Mount Etna (Italy) in the formation of new particles in the size range of 2.5–10 nm through the gas-to-particle nucleation of sulfuric acid (H2SO4) precursors, formed from the oxidation of SO2, and their evolution to particles with diameters larger than 100 nm. Two simulations were performed using the Weather Research and Forecasting Model coupled with chemistry (WRF-Chem) under the same configuration, except for the nucleation parameterization implemented in the model: the activation nucleation parameterization (JS1 = 2.0 × 10−6 × (H2SO4)) in the first simulation (S1) and a new parameterization for nucleation (NPN) (JS2 = 1.844 × 10−8 × (H2SO4)1.12) in the second simulation (S2). The comparison of the numerical results with the observations shows that, on average, NPN improves the performance of the model in the prediction of the H2SO4 concentrations, newly-formed particles (~2.5–10 nm), and their growth into larger particles (10–100 nm) by decreasing the rates of H2SO4 consumption and nucleation relative to S1. In addition, particles formed in the plume do not grow into cloud condensation nuclei (CCN) sizes (100–215 nm) within a few hours of the vent (tens of km). However, tracking the size evolution of simulated particles along the passive plume indicates the downwind formation of particles larger than 100 nm more than 100 km far from the vent with relatively high concentrations relative to the background (more than 1500 cm−3) in S2. These particles, originating in the volcanic source, could affect the chemical and microphysical properties of clouds and exert regional climatic effects over time.