Sialolithiasis is a disorder of the salivary glands characterized by the presence of mineralized structures. The aim of this article is to contribute to the understanding of the etiopathogenesis of sialolithiasis based on data reported in the literature and the interpretation of scanning electron microscopic (SEM), histopathologic, fluorescence, and energy-dispersive X-ray spectroscopic (EDX) studies. The results of these analyses in a single case are presented. Fluorescence microscopy captured saliva flowing inside a giant sialolith, EDX analysis enabled the quantification of samples of minerals and characterized the chemical composition in the internal areas of the sialolith, and SEM images captured the external communications of the sialolith (ostia). Many theories have been proposed to explain sialolithiasis development, but few consider the role of saliva in its dynamic form. The authors propose that the triple synergism of microbiota, biofilm, and salivary dynamics plays a fundamental role in the development and intrinsic architecture of sialoliths, creating a cyclic sialolithic mineralization. This hypothesis is supported by the results of the laboratory studies in the present case.