A television news magazine called "In Focus" is airing a profile of Monk, and Monk is at the home of the show's host, James Novak, for a viewing party. Natalie, Stottlemeyer, and Disher are all there to celebrate Monk's big television debut. "In Focus" follows Monk as he tries to solve his one hundredth case, and the show is interspersed with interviews of Monk's friends, family, and even some of the criminals he's helped put away over the years.

As shown on "In Focus," the case begins when Monk is called to investigate the death of an aspiring actress who's been strangled to death in the lobby of her apartment building. Monk notices that the victim's lipstick is missing from her purse, and after some more investigation, he deduces that the victim knew the person who killed her.

Unfortunately, there are no leads in the case, and days later another young actress is murdered, also strangled. Again, there are no signs of forced entry, and again the victim's lipstick is missing. The two victims both worked at the same restaurant, but a trip to the establishment turns up nothing. The case continues to confound when a third young woman turns up dead. It's another actress, killed the same way, but there appears to be no connection between this latest victim and the previous two. Then, Monk makes a keen observation: all three women had head-shot photos taken by the same photographer, a man named Douglas Thurman.