HIV-associated PBL is an AIDS-defining cancer, classified by WHO as distinct entity of aggressive DLBCL. To date less than 250 cases have been published, of them17 are pediatric. The pathogenesis of this rare disease is related to immunodefiency, chronic immune stimulation and EBV. Clinically is a rapid growing destructive disease mainly of oral cavity, but frequently involves extraoral and extranodal sites. The diagnosis requires tissue mass or lymph node biopsy, but core needle or fine needle biopsy is acceptable for difficult access sites. Immunophenotype is CD45, CD20, CD79a negative and CD38, CD138, MUM1 positive, EBER and KI67 is >80%. Frequently is diagnosed in patients with low CD4+ and high viral load, however is reported also in patients on effective cART and high CD4. Treatment administered is usually CHOP or CHOP-like regimens, more intensive regimens as CODOX-M/IVAC or DA-EPOCH are possible options. Intensification with ABMT in CR1 may be considered for fit patients. Rituximab is not useful for this CD20- disease. Bortezomib and new drugs were used at case report level, with transient response. CNS prophylaxis is mandatory. Use of cART is recommended during chemotherapy, keeping in mind the possible overlapping toxicities. For refractory/relapsed patients, therapy is usually considered palliative, however in chemosensitive disease intensification + ABMT or new drugs may be considered. Factors affecting outcome are achieving complete remission, PS, clinical stage, MYC , IPI. Reported median PFS ranges between 6-7 months and median OS ranges between 11-13 months. Long term survivor are reported but mostly in pediatric patients. Due to the scarcity of data on this subtype of NHL we suggest that the diagnosis and the management of HIV-positive PBL patients should be performed in specialized centers.