Toughest case I can think of? Woman gets drugged by her doctor and raped. When the woman goes to the police, they get the doctor to give them a blood sample to check against a rape kit.
Blood sample doesn’t match. Years later the doctor gets caught molesting his own daughter. When brought in to police, it’s revealed he had surgically implanted a plastic tube full of someone else’s blood into his arm, and made sure the person drawing the blood for the rape kit test drew from that tube. When the rape kit test is compared to his actual blood, it’s found as a match.