Human immunodeficiency virus (HIV) infection is associated with an increased risk of malignant disease. However, a case of diffuse large B-cell lymphoma arising in the submandibular gland in a patient with HIV infection has never been reported. This report describes a case of a patient with HIV infection and HIV-associated lymphadenopathy who developed diffuse large B-cell lymphoma (DLBCL) arising in the submandibular gland. Both the submandibular gland and its regional lymph nodes were positive by positron emission tomography/computed tomography (PET/CT), which led to radical neck dissection. The pathological diagnosis was DLBCL in the submandibular gland, however, that of regional lymph nodes was HIV-associated lymphadenopathy and was not malignancy. PET/CT-based staging can make a false-positive result in lymph nodes of patients with HIV infection due to HIV-associated lymphadenopathy.