Nanomaterials are increasingly being used for commercial purposes. However, concerns about the potential risks of exposure to humans have been raised. We previously reported unusual pulmonary disease and death in a group of patients with occupational exposure to spray paint. However, the nanoparticle and chemical composition of the exposure was not fully described. The present study aimed to isolate and identify the nanoparticles observed in the patients' biopsies and report the potential deleterious effects to human lungs using electron microscopy. Using electron microscopy and energy dispersive x-ray analysis, silica nanoparticles were identified and characterized mainly in macrophages, pulmonary microvessels, vascular endothelial cells, microlymphatic vessels, pleural effusions, and a few in alveolar epithelial cells and pulmonary interstitial tissue (with no microscale particles present). Notably, damage to alveolar epithelial cells, macrophages, vascular endothelial cells, and the blood-gas barrier was observed. Given the well-documented toxicity of microscale silica, it is possible that these silica nanoparticles may have contributed in part to the illness reported in these workers. Such a possibility supports the adoption of controls and prevention strategies to minimize inhalation of nanoparticles by workers, and it highlights the urgent need and the importance of the nanosafety study in humans.