Thrombotic microangiopathy (TMA) is defined by the typical triad of severe thrombocytopenia, hemolytic anemia and endorgan dysfunction and can be characterized by the pathophysiology of ischemia-inducing microthrombi in arterioles and capillaries possibly leading to severe organ dysfunction up to acutely life-threatening endorgan damage. In terms of etiology, management, therapy and prognosis, the following manifestations are distinguished: thrombotic thrombocytopenic purpura (TTP), shigatoxin-induced hemolytic-uremic syndrome (STEC-HUS), secondary comorbidity-related TMA and atypical hemolytic-uremic syndrome (aHUS). We present the case of a 49 year old lung transplant recipient developing aHUS. The complexity of the underlying pathomechanisms of TMA, the complicated differentiation of each TMA manifestation and the complex management of aHUS in the post-transplant setting illustrate the uniqueness of this patient case.