Abjective To investigate induction of B-cell specific phenotype in classical Hodgkin lymphoma (cHL) upon All-Trans Retinoic Acid (ATRA) incubation. Methods Construction of B-cell specific promoter (CD19, CD79a, CD79b) driven reporter plasmid with NEO cassette to realize stable transfection and selection of cHL reporter cells. Verification of intact integretion by amplification of the promoter and luciferase sequences. Functional validation of the B-cell specific promoter by ABF1 interference and luciferase assay. Repoter cells were incubated with various dose of ATRA and luciferase activity was detected at 24, 48 and 72 hours. Reporter cells were single or combinational treated with 5-Aza and ATRA followed by luciferase assay. Detection of endogenous B-cell specific genes (CD19, CD20, CD79a and CD79b) transcription and expression level respectively by Real-time PCR and immunoblot. Measurement of expression level of CD30 antigen on Hodgkin lymphoma cell memberance upon ATRA by Flow Cytometry. Results ATRA treatment stimulated B-cell specific signature in cHL cells including CD19, CD79a and CD79b while down regulated their CD30 expression. Conclusions ATRA induces B-cell phenotype deficient cHL cells regain their B-cell transcriptional program while abolish their Hodgkin-specific machinery.