<p>Poisoning of companion animals resulting from exposure to analgesics intended for human use is a frequent and clinically relevant problem in veterinary practice, usually associated with administration without professional supervision. This can induce severe systemic toxicity. Diagnostic confirmation can be particularly challenging in cases presenting with nonspecific clinical signs or when conventional biological samples are unavailable. This case report describes the innovative use of earwax as a non-invasive biological matrix for toxicological confirmation in veterinary medicine. A 9-year-old male mixed-breed dog was admitted following a traumatic accident and subsequent administration by its owner of a human medication containing acetaminophen and codeine. Clinical evaluation revealed lethargy, hypersalivation, hyporexia, dehydration, and neurological abnormalities. Laboratory findings demonstrated neutrophilic leukocytosis and marked increases in hepatic enzyme activities, consistent with acute hepatocellular injury. Toxicological investigation using headspace gas chromatography–mass spectrometry detected acetaminophen-related signatures in an earwax sample, supporting suspected exposure to the drug. Intensive treatment was promptly initiated and included fluid therapy, antidotal treatment with N-acetylcysteine, opioid antagonism, analgesia, and supportive care. The patient showed progressive clinical improvement, with complete resolution of clinical signs and full recovery. This case highlights the significant risks of administering human medications to companion animals and underscores the need to improve owner awareness of self-medication practices. Furthermore, it demonstrates the diagnostic potential of earwax as a non-invasive biological matrix for toxicological confirmation, expanding the range of complementary diagnostic tools available for veterinary toxicology and supporting improved clinical decision-making in cases of suspected pharmaceutical intoxication.</p>