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Background: Drug toxicological screening is commonly used as a diagnostic tool in patients with suspected toxic ingestion. False positive results due to cross-reactive compounds in drug assays may lead to misdiagnosis and mismanagement, especially when child abuse is suspected., Case Report: Two of our patients with history of ingestion of carbamazepine were tested positive on screening with the tricyclic antidepressant immunoassay. The immunoassay's known cross-reactivity for carbamazepine is reportedly as low as 0.3%. Plasma samples of our patients were initially considered positive for tricyclic antidepressants because the cross-reaction of carbamazepine gave tricyclic antidepressant concentrations as imipramine equivalent sufficiently above the assay cut-off point (20 ng/mL). Later, confirmatory urine testing of both patients using high-performance liquid chromatography was negative for tricyclic antidepressants., Conclusion: This interference has significant clinical implications, and can be avoided on urine testing using a specific chromatographic assay such as high-performance liquid chromatography.