Objective To investigate the induction of B?cell specific phenotype in classical Hodgkin lymphoma (cHL) upon all?trans retinoic acid (ATRA) incubation. Methods To construct B-cell specific promoter ( CD19, CD79a, CD79b) driven reporter plasmid with NEO cassette to realize stable transfection and selection of cHL reporter cells. To verify the intact integration by amplification of the promoter and luciferase sequences, and to functionally validate the B-cell specific promoter by ABF1 interference and luciferase assay. Repoter cells were incubated with various doses of ATRA and luciferase activity was detected at 24, 48 and 72 hours. Reporter cells were treated alone or in combination with 5-Aza and ATRA followed by luciferase assay. Endogenous B-cell specific genes (CD19, CD20, CD79a and CD79b) transcription and expression levels were detected by real-time PCR and immunoblot, respectively. The expression level of CD30 antigen on Hodgkin lymphoma cell membrane upon ATRA was assessed 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 to regain their B-cell transcriptional program while abolishes their Hodgkin-specific machinery.