Los Anticuerpos (Ac.) Anti-Sm son específicos para el diagnóstico de Lupus eritematoso sistémico (LES) pero infrecuentes. Frente a una enfermedad autoinmune sistémica probable varias guías recomiendan un protocolo escalonado de estudio, que en la práctica clínica no siempre se cumple. El laboratorio de la “Asociación Española” (Montevideo-Uruguay), comenzó a utilizar el método de quimioluminiscencia (CLIA), observando en ocasiones reactividades Anti-Sm no esperadas. Los objetivos fueron determinar el “cut-off” óptimo del método de CLIA y comparar su desempeño diagnóstico con el ELISA para Ac. Anti-Sm. Se comparó el “cut-off” del CLIA con respecto al ELISA e Inmunofluorescencia indirecta (IFI, ANA HEp-2) utilizando un material de referencia. Se determinaron los Ac. Anti-Sm por método de CLIA y ELISA en 40 sueros de pacientes. Se calculó la sensibilidad, especificidad, valor predictivo positivo (VPP), negativo (VPN) y el “cut-off” óptimo del CLIA (curva ROC). Se calculó el chi 2, el coeficiente kappa (Cohen) y el R2 entre el CLIA y el ELISA. Los “cut-off” hallados fueron: IFI 1/4096, CLIA 1/1024 y ELISA 1/512. La sensibilidad del CLIA y ELISA fue 95%, y la especificidad: 93% y 100% respectivamente; El VPP del CLIA y ELISA: 76% y 100%, y el VPN 93% y 95%.respectivamente. El “cut-off” óptimo del CLIA fue 41.5 CU (Sensibilidad 85% y Especificidad 95%), el chi 2 de 18.2 (p: < 0.01), el coeficiente kappa de 65% (p: < 0.01) y un coeficiente R2 de 0,83 (p: 1,92 x 10 -16). El CLIA puede ser utilizado como una alternativa al ELISA para la búsqueda de Ac. Anti-Sm ajustando el “cut off” del método a la población de cada laboratorio utilizando el método IFI, ANA HEp-2 en paralelo o en forma escalonada.Anti-Sm Antibody (Ab.) is a specific marker for Systemic Lupus Erythematosus, although unusual. Several guidelines recommend a phased study protocol if a systemic autoimmune disease is suspected, although in clinical practice this is not always fulfilled. The “Asociación Española”´s laboratory (Montevideo-Ururguay) started to use the chemiluminescence method (CLIA) for Anti-Sm determination and sometimes unexpected reactivities were observed. The aim was determine the CLIA´s optimal cut-off and compare it´s diagnostic performance against the ELISA method for Anti-Sm Ab. The CLIA´s and ELISA´s cut-off for Anti-Sm Ab. were compared with the HEp-2 indirect immunofluorescence (IIF) method using a reference material. Sera from 40 patients were screened for Anti-Sm Ab by CLIA and ELISA methods. Sensitivity, specificity, negative (NPV) and positive predictive values (PPV) for the CLIA method for Anti-Sm Ab optimal cut-off were calculated as well (ROC plots). The association and the degree of agreement between ELISA and CLIA methods were evaluated (chi 2and Cohen’s kappa coefficient respectively) as the R2 coefficient was also calculated. The cut off values of the three methods were: 1/4096 IIF, 1/1024 CLIA and 1/512 ELISA. The CLIA and ELISA sensitivities were equal (95%) while the specificities were 93% y 100% respectively; PPV and NPV for CLIA method were 76% and 93%, and for ELISA 100% and 95%. The optimal cut-off for CLIA method was 41.5 CU (85% sensitivity and 95% specificity). The chi 2 value was 18.2, p: < 0.01, the Cohen’s kappa coefficient: 65%, p: < 0.01, and the R2 coefficient: 0.83 (p: 1,92 x 10 -16). Anti-Sm Ab by CLIA method can be used adjusting the cut-off value for each laboratory population, using IIF method in parallel or using a stepped protocol.