Dermal fillers are widely used for facial rejuvenation and reconstruction and present fewer risks than surgical approaches. Nevertheless, several complications may occur, including nodule formation. A nodule is a clinical sign corresponding to different etiologies, such as overcorrection, infection, allergic reaction, or granuloma. However, their treatment represents a diagnostic challenge. We present a retrospective review of 26 consecutive patients who underwent a biopsy for facial nodule formation more than 3 months after filler injections, to determine the diagnosis of the nodule and type of filler used. All patients were women (mean age, 57.8 years). Some patients suffered from different localizations: lip, 14 cases; nasolabial folds, 6; cheeks, 5; infraorbital region, 5; the glabella, 2; the temporal region, 1; and chin, 1 case. Only 5 (19.2%) patients knew the type of filler used, and in another 4 cases, the injector was able to provide some information. In 65.4% of cases, the filler type was unknown. Histopathological analysis revealed a "granulomatous" nodule in 30 sites and a "non-granulomatous" nodule in 4 cases. Concerning the type of filler, 5 different histopathological patterns were found. Our results demonstrate that a clinical history and histopathological analysis whether to confirm or not to confirm the diagnosis of granuloma and to identify the type of filler are essential tools to achieve an accurate diagnosis of the problem-oriented treatment of nodules after dermal filler injections. We propose an algorithm for the management of nodules after filler injection.