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Acute abdominal pain is one of the most common chief complaints encountered in the emergency department and outpatient setting. Across all sites, the left upper quadrant (LUQ) is the least common location for abdominal pain with reportedly the lowest physical examination interrater agreement. The limited sensitivity of physical examination, combined with an uncommon and nonspecific clinical presentation, make assessment of LUQ pain challenging. Acute LUQ pain may arise directly from the spleen or infections in the LUQ, or represent referred pain from other organs such as stomach, bowels, pancreas, or kidney. This document aims to address acute pain with suspected splenomegaly, with fever, and not otherwise specified. CT abdomen and pelvis with contrast is usually appropriate for detection of a broad range of pathologies. In patients with suspected splenomegaly, ultrasound abdomen is also usually an appropriate alternate for initial imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.