There are three subtypes of T-prolymphocytic leukemia (T-PLL) based on their cytogenetic presentations, all of which share a similar immunophenotype. This chapter discuss their immunophenotype in detail. Occasional cases with atypical immunophenotypes, such as negative CD3 or CD45 expression, are also described. Tumor heterogeneity, with populations displaying different immunophenotypes, is discussed, along with immunophenotypic shift. Differential diagnosis is addressed, with a focus on the challenges in distinguishing TCL1-family negative T-PLL from other leukemic T-cell lymphomas/leukemias.