Background: Diarrhea is common among patients with cancer, and rapid diagnosis of gastrointestinal (GI) infections using a multiplex stool enteric pathogen panel (EPP) may expedite clinical decision-making and inform infection prevention measures. However, the diagnostic yield of EPPs in patients with cancer with hospital-onset diarrhea is not well defined. At our center, inpatient diarrhea testing guidelines recommend EPP testing primarily in those with community-onset diarrhea. We aimed to assess adherence to these EPP testing guidelines and describe EPP diagnostic yield in hospitalized patients with cancer to identify opportunities for diagnostic stewardship. Methods: We retrospectively reviewed EPP and stand-alone C. difficile (SACD) tests ordered between July 1, 2021 – May 23, 2025 among hospitalized patients (age ≥18 years) with a malignancy diagnosis. Our center recommends EPP testing (BIOFIRE® FILMARRAY® GI Panel) for community-onset diarrhea (on or before hospital day [HD] 3) and SACD testing for hospital-onset diarrhea (after HD 3). EPPs may be ordered after HD 3 for patients with unexplained prolonged or bloody diarrhea. Results: A total of 3338 stool tests (1433 EPP, 1905 SACD) were performed among 2131 patients. Among EPPs, 468 (33%) were ordered after HD 3 whereas 1621 (85%) SACD tests were ordered after HD 3 (Figure 1). The proportion of EPPs ordered after HD 3 was highest among patients with hematologic malignancies (44%) compared to other cancer types and higher among hematopoietic cell transplant (HCT) recipients versus non-HCT recipients (54% vs. 22%; Figure 2). Among EPPs ordered after HD 3, 102/468 (22%) were positive for ?1 pathogen compared to 288/965 (30%) EPPs ordered on HD 1-3. At least 1 non-C. difficile pathogen was detected in 49/468 (10%) EPPs ordered after HD 3 compared to 146/965 (15%) on HD 1-3 (Table 1). Among EPPs with non-C. difficile pathogens detected after HD 3, norovirus was most frequent (26/468; 6%; Table 1). Conclusion: EPP detection of non-C. difficile pathogens among hospitalized patients with cancer was lower in patients with hospital-onset diarrhea compared to those with community-onset diarrhea. Most EPP orders after HD 3 at our center occurred in HCT recipients and patients with hematologic malignancies. Additional studies are needed to determine the clinical significance of positive EPP results beyond HD 3 and understand which patients may benefit most from EPP testing beyond HD 3.