Key Clinical MessageGranulomatosis with polyangiitis (GPA), a rare form of small vessel vasculitis, may be manifested by multisystem involvement misleading its definitive diagnosis. The involvement of salivary glands is a very rare characteristic of GPA. Herein, we described a case of GPA with submandibular salivary gland involvement followed by reviewing the literature on similar cases. The case was a 31‐year‐old man, a known case of seronegative peripheral arthritis that referred recently with bilateral enlargement of the parotid and submandibular glands. Pulmonary nodules were also evident in the patient's CT scan. Fine‐needle aspiration under ultrasound guidance indicated the presence of degenerated squamoid cells, giant cells, and inflammatory cells with a priority of neutrophils in the submandibular gland, as well as the presence of a cyst containing fluid without the evidence of malignancy in the parotid gland. The positivity for the Anti‐neutrophil Cytoplasmic Antibody (C‐ANCA) marker was also revealed. The patient was treated with methotrexate, prednisolone, and rituximab which led to a gradual reduction in the size of the glands and the improvement of the patient's clinical symptoms within 1 month after the treatment. Enlargement of salivary glands in the context of inflammatory disorders can raise doubts about the existence of GPA, and therefore imaging evaluation and histopathological assessment with an ANCA test will be necessary to confirm or rule out it.