We compared the frequency of gastrointestinal (GI) pathogen detection in an oncology patient population by two multiplexed molecular assays, the Luminex xTAG® GI Pathogen Panel (GPP, which identifies 14 GI pathogens) and the BioFire GI pathogen panel (BFGP, which identifies 22 GI pathogens). We additionally reviewed the clinical characteristics of patients tested with both panels. A total of 200 prospectively collected and 81 archived stool samples were tested by both panels. In the prospective cohort, the GPP and BFGP identified a pathogen in 33.5% (95% CI: 27.3–40.35%) and 39.6% (95% CI: 33.0%–46.6%) of samples respectively (p=0.25). The BFGP detected significantly more pathogens than the GPP (p=0.038) with 21.3% of samples positive for targets only detected by the BFGP. The concordance between the assays was very good at 91.1% (κ=0.8, 95% CI=0.7–0.9) when considering only pathogens detected by both assays. The most frequent pathogens detected were Clostridium difficile, Norovirus, Campylobacter and Salmonella species. On the archived samples, the BFGP was positive in 92.6% of samples but detected more pathogens than the GPP (86 vs 97, p=0.033), including both targets unique to the BFGP and targets common to both panels. A pathogen was more frequently detected in patients with hematological malignancies than solid tumors and in ambulatory patients compared to hospitalized patients but these differences were not statistically significant. Overall, the detection rates were similar for both the GPP and the BFGP and the latter detected more than one pathogen in additional patients. The impact of increased detection of GI pathogens by multiplexed panels on the clinical care of oncology patients will require further investigation.