Thrombotic microangiopathy (TMA) is most of the time caused by thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. A 60-year-old female was diagnosed in 2014 with mammary breast adenocarcinoma treated by several-line therapy: mastectomy, docetaxel, cyclophosphamide, radiotherapy, doxorubicine, and capecitabine. By mid-November, the patient was admitted to the hospital with regenerative, mechanical, and hemolytic anemia, schistocytes at 3%, and thrombopenia (99 G/L), associated with high blood transfusion requirement. After 9 sessions of plasmapheresis, there was no significant improvement in the biological parameters, nor after 2 cycles of paclitaxel. The patient was then treated with eculizumab during 4 weeks, with a slight reduction in blood requirement, and simultaneously with palbociclib. Since being treated with palpociclib, she had a great reduction in blood requirement and a good clinical condition. To conclude, we reported an initial moderate improvement of paraneoplasm-related TMA syndrome under eculizumab therapy with a slight reduction in red blood cell requirement; however, palbociclib therapy achieved a very good response with a dramatic reduction in red blood cell requirement.