A serial can disprove authenticity but never establish it. If the engraving uses a prefix Rolex never issued, if it dates to an era before the reference existed, or if it is etched shallowly instead of crisply machined into the case, you have a counterfeit or a re-cased watch. None of those checks work in reverse: a plausible-looking serial is exactly what a good fake carries, because it was copied from a real watch.
Serial and reference also have to agree. A 2015 Submariner reference wearing a 1990s prefix means the case, the bezel, or the whole watch has been swapped. Our 11-point authenticity checklist walks through the physical tells that actually hold up, and the reference number guide explains how to read the model number so you can cross-check the two.
If a serial appears on a watch you are considering buying, run it against The Watch Register and Chrono24's stolen-watch database before any money moves. Both are free to search and both cover serials reported stolen.