TEMPI (telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal 
gammopathy, perinephric fluid collections, intrapulmonary shunting) syndrome is 
a newly described clinical entity that is generally considered a plasma cell 
dyscrasia with multiple system involvement. The etiology and pathophysiology of 
this condition remains elusive. Nevertheless, clonal plasma cells and monoclonal 
protein appear to be major contributors. The early diagnosis of TEMPI syndrome 
is essential because therapies targeting the underlying plasma cells can lead to 
a dramatic response. Bortezomib-based chemotherapy, daratumumab monotherapy, and 
autologous hematopoietic stem cell transplantation can result in reversal of 
most manifestations. Nevertheless, the diagnosis of TEMPI syndrome remains a 
substantial challenge owing to its rarity and the complexity of clinical 
presentations. TEMPI syndrome is often misdiagnosed as other causes of 
erythrocytosis, resulting in a delayed diagnosis and further clinical 
deterioration. The aim of the present review was to present the clinical and 
biologic features of TEMPI syndrome, highlighting the differential diagnosis and 
outlining the present understanding of its pathophysiology and treatment.