Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe and most common autoimmune encephalitis in patients under 40 years old. Anti-NMDAR encephalitis has various clinical and neuroimaging findings. Here we report a special case of an anti-NMDAR encephalitis who had diffuse lesions in bilateral hemispheres with mild mass effects in left basal ganglia area. Case presentations: A 28-year-old female anti-NMDAR encephalitis patient mainly presented with headache and fever. Brain magnetic resonance image (MRI) showed slightly contrasted diffuse lesions, involving the left temporal and frontal lobes, left basal ganglia area and splenium of corpus callosum, as well as the right frontal lobe, with mild edema surrounded in the left basal ganglia area. Cerebrospinal fluid (CSF) revealed a moderate pleocytosis with normal protein and glucose levels. Anti-NMDAR antibodies were identified in CSF. Transvaginal ovarian ultrasound did not reveal an ovarian teratoma. The patient was treated with immunoglobulin and steroid, and had a good recovery. Conclusions: Anti-NMDAR encephalitis has no special clinical manifestations and brain MRI is highly variable, which could be unremarkable or abnormal involving white and grey matters. The extensive lesions in frontal and temporal lobes, and basal ganglia area, with mild mass effects, have not been described previously. Recognition of various changes in brain MRI will enable the early detection of anti-NMDAR antibody and then effective treatments.