Objective: To analyze the clinical, radiological and laboratory features of suspected MS/CIS patients with positive serology for antiphospholipid antibodies (APLAb) and discuss its meaning. Background The frequency of APLAb in MS is higher than the general population, although several prevalences have been reported. The value of these findings is controversial and its meaning unknown. Design/Methods: A retrospective study of the patients admitted to our department during the last three years with suspected MS/CIS. Clinical, MRI and laboratory test were conducted. APLAb determination included anti-B2-glycoprotein-I (B2GPI) and anti-cardiolipine (ACL) IgM/IgG. APLAb titres: 1-10 U/ml=negative, 10-40 U/ml=weak positive, 40-80 U/ml=moderate positive, >80 U/ml=strong positive. Results: From 90 patients attended with MS suspicion, five had APLAb positive titres. Patient 1: 20 year-old woman. Diplopia. MRI-T2-lesions=12. CSF normal. B2GPI-IgM and ACL-IgM weak positive. Rest of study normal/negative. Final diagnosis=CIS. Patient 2: 44 years-old woman. Optic Neuritis. MRI-T2-lesions=7. CSF normal. B2GPI-IgM weak positive. Rest of study normal/negative. Final diagnosis=CIS. Patient 3: 29 years-old man. Cognitive declination. MRI-T2-Lesions=10. CSF normal. B2GPI-IgG and ACL-IgG weak positive. Rest of study normal/negative. Final diagnosis=CIS. Patient 4: 48 years-old man. Optic Neuritis. MRI-T2-lesions=10. CSF normal. B2GPI-IgG strong positive and ACL-IgG moderate positive in two 6-months separated determinations. Rest of study: Altered salivary glands gammagraphy and Schimer test, anti-SSA/RO 34U/ml, ANA 1/320. Final Diagnosis= primary Sjogren syndrome. Patient 5: 48 year-old man. MRI-T2-lesions=20. CSF: 40 leucocytes, normal glucose and proteins, IgG-Index 3.5. Positive oligoclonal bands. ACL-IgM strong positive, B2GPI-IgM moderate positive, ACL-IgG and B2GPI-IgG weak positive in two 6-months separated determinations. Rest of study: lymphopenia, mouth ulcers, DNAds 30U/ml, ANA 1/320. Final diagnosis: Neurolupus. Conclusions: The real significance of APLA in MS is still uncertain. However, persistently high titres along with atypical features, should raise suspicion that MS is not present. We believe in the utility of APLA in the differential diagnosis of MS/MS-like. Disclosure: Dr. Rodriguez Cruz has nothing to disclose. Dr. Cuello has nothing to disclose. Dr. Perez Sanchez has nothing to disclose. Dr. Martinez Gines has nothing to disclose. Dr. De Andres has nothing to disclose.