BACKGROUND & AIMS: We evaluated the efficacy of rituximab in patients with anti-TS-HDS, anti-FGFR3 and anti-plexin D1 small fiber neuropathy (SFN) who failed to respond to conventional treatments and immunotherapy. METHODS: We reviewed 111 patients diagnosed with SFN - 83 definite SFN, 9 had positive antibody titers towards TS-HDS, FGFR3 or plexin-D1 and received symptomatic treatment, in addition to trials of intravenous immunoglobulin (IVIg) and/or corticosteroids. Five patients who failed to respond were offered rituximab (two intravenous 1 g infusions, two weeks apart). Clinical parameters and questionnaires were compared. RESULTS: Two patients were positive for anti-TS-HDS, one for anti-plexin D1 and two for anti-FGFR3 antibodies. Therapeutic efficacy was assessed by circulating CD19 INTERPRETATION: This study illustrates the efficacy and potential role of anti-CD20 monoclonal antibody in antibody-associated immune SFN, especially in those who fail to respond to IVIg or corticosteroid. Further randomized controlled trials and larger prospective studies are needed to determine the effectiveness and safety of Rituximab in seropositive patients with SFN.