OBJECTIVES: To describe cases of PML in FAERS for recently approved biological and targeted cancer therapies (BTCT) and to calculate safety signals for PML METHODS: The FDA website was searched for BTCT approvals from 2009 to 2015. With each BTCT as the suspect drug, the FAERS was searched for all cases of PML.  For BTCTs with >2 cases of PML, the proportional reporting ratio (PRR) and its 95% confidence interval (CI) and the associated chi square was determined.  PRR provides a data mining signal of disproportionate reporting in FAERS.  Case narratives were obtained through FDA Freedom of Information requests.  Cases were summarized for demographic and clinical information. RESULTS: New BTCTs included 48 drugs. Of these 17 (35.4%) drugs had FAERS PML cases (n=82).  Of the PML cases among BTCTs, 21 (25.6%) included rituximab as a secondary suspect drug.  Significant PRR signals were found among 7 (14.6%) drugs: alemtuzumab (9.9, CI:6.0-16.4), belimumab (4.5 CI:2.3-9.0), brentuximab (24.5, CI:14.8-40.6), ibrutinib (5.6 CI:3.0-10.5), idelalisib (4.1, CI:1.3-12.6), obinutuzumab (7.4, CI:2.4-22.8), ofatumumab (16.3, CI:9.6-27.4).  Among drugs with significant signals, the rates of PML cases versus all FAERS cases for each drug ranged from 1.47% (brentuximab) to 0.27% (belimumab), compared to 0.04% for all FAERS data and 35 (51.5%) of the 68 cases were confirmed by magnetic resonance imaging and positive John Cunningham Virus in cerebro-spinal fluid.  If documented, mean months from first dose to event was shortest for brentuximab (3.1) and belimumab (4.3) and longest for ofatumumab (13.7).   A limitation of FAERS data is that missing data are common. CONCLUSIONS: Clinicians and patients should be involved in risk-benefit assessment of the possibility of PML associated with BTCTs, particularly when used in combination with other drugs which may cause PML, such as rituximab, or for illnesses such as chronic lymphocytic leukemia where PML is not uncommon.