This guide provides a rapid diagnostic workflow for cell culture contamination, helping researchers quickly determine whether observed culture abnormalities are caused by contamination. It outlines common observable signs, such as turbidity, abnormal morphology, odour changes, or inconsistent cell behaviour, and links them to likely contamination categories including bacteria, fungi, mycoplasma, viruses, endotoxins, and chemicals. For each scenario, it recommends practical diagnostic actions like Gram staining, PCR, ELISA, LAL assays, and STR profiling, offering a concise reference to guide troubleshooting and ensure culture integrity.