We report here the case of a 50-years-old man treated for mixed ă connective tissue disease (MCTD) positive for anti-U1 ribonucleoprotein ă (U1RNP) antibodies who secondarily developed a granulomatosis with ă polyangiitis (GPA) associated with anti-proteinase 3 anti-neutrophil ă cytoplasmic antibodies (PR3-ANCA). We then evaluated the frequency of ă the association between anti-U1RNP and anti-PR3-ANCA antibodies by a ă systematic retrospective study in ten European hospitals. Overall, out ă of 11,921 samples analyzed for both auto-antibodies, 18 cases of ă anti-U1RNP and anti-PR3-ANCA double positivity were found and only one ă patient presented with both MCTD and GPA symptoms. Our retrospective ă analysis indicates that anti-U1RNP and anti-PR3-ANCA antibodies double ă positivity is infrequent and very rarely associated with both MTCD and ă GPA. Our observation describes for the first time the coexistence of ă MTCD and severe GPA in a Caucasian patient. Association of anti-U1RNP ă and ANCA antibodies was rarely reported in the literature. Eleven cases ă of MCTD and ANCA vasculitis have been reported to date, with only two ă cases with anti-PR3-ANCA association, and only one vasculitis. The seven ă other cases reported in the literature presented with an association of ă MCTD and microscopic polyangiitis which appears to be a more frequent ă presentation than MTCD associated with GPA.