New psychoactive substances (NPS) continue to emerge around the world. APP-BINACA (or APP-BUTINACA), a novel synthetic cannabinoid, was first reported in Europe in January 2019 and later in the United States in March 2019. APP-BINACA was identified in the United States for the first time in blood sample extracts from forensic casework by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). To date, APP-BINACA has been identified in 11 forensic toxicology cases from five states and in both medicolegal death investigations and drug impaired driving investigations. APP-BINACA was commonly found in combination with 4F-MDMB-BINACA. Subsequent to its discovery in biological samples, APP-BINACA was detected and characterized in seized drug material by gas chromatography mass spectrometry (GC–MS), LC-QTOF-MS, and nuclear magnetic resonance (NMR) spectroscopy. Further analysis of biological specimens resulted in the identification of five metabolites, including 4-HO-APP-BINACA and APP-BINACA 3-phenylpropanoic acid. The frequency of APP-BINACA detection appears to be increasing and this new synthetic cannabinoid has been identified as a possible contributory factor in adverse events, including death. Since it is not widely tested for, it is not yet known the extent to which APP-BINACA is contributing to morbidity and mortality, but forensic scientists, public health officials, and others should be aware of its possible presence and impact. Laboratories should incorporate APP-BINACA into testing workflows for detection and confirmation, where possible. (publisher abstract modified)