Objective: The aim of this paper is to report 2 cases with overlapping syndromes in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Methods: Antibodies were detected by indirect immunofluorescence assay. Patient data were analyzed retrospectively. Results: One patient presented with overlapping neuromyelitis optica spectrum disorder (NMOSD) and positive GFAP-IgG and aquaporin-4-IgG. His main symptoms included vision loss, hiccups, fever, headache, and ataxia. High leukocyte count and protein levels were found in cerebrospinal fluid. Brain magnetic resonance imaging (MRI) revealed abnormalities in the hippocampus, midbrain, pons, medulla, and meninges. Characteristic radial enhancing patterns were seen. The other patient was a male with relapsing polychondritis (RP) and positive GFAP-IgG. His main manifestations were meningoencephalitis and dementia. MRI showed extensive abnormalities in the white matter around the ventricles, temporal lobe, and thalamus, with enhancement. Both patients responded well to the treatment with steroids and immunosuppressants. Conclusions: Although overlapping syndromes are rare, we report positive GFAP-IgG in 2 cases with NMOSD or RP. Both patients had clinical features of GFAP astrocytopathy, but diagnosis of the condition was very challenging because of the overlapping presentation.