Spot was a relatively fickle cat. She only took to Data and Reginald Barclay. In 2369, while taking care of Spot, Commander Riker was forced to go to sickbay when she scratched his face. The next year, Geordi La Forge borrowed Spot, since he wanted to see what having a pet cat was like. They did not get along well, either. A short time later, Data unsuccessfully tried to train Spot, which prompted La Forge to joke that it was actually Spot who was successfully "training" Data. On another occasion, Worf tried to give Spot commands, but Spot would not obey them. Data made 221 different formulas of food for Spot, many of which Spot did not care for. Later that year, Spot became pregnant by one of the twelve male cats aboard the Enterprise-D at that time.

In 2370, Spot played an integral part in saving the crew of the Enterprise-D. A synthetic T-cell became airborne and infected the crew, causing inactive parts of their genetic code to activate and essentially "de-evolve" them. Data and Picard returned from an away mission to the chaotic situation. They made it to Data's quarters, where Spot transformed into an iguana. Her kittens, just recently born, were unaffected, due to the natural defense mechanisms in the placenta which protects infants from the mother's diseases while in the womb. This led to Data develop a cure using amniotic fluid from Nurse Ogawa, who was also pregnant.

In 2371, Spot survived the destruction of the Enterprise-D. Data, via his newly-installed emotion chip, cried tears of joy over Spot's survival. In 2379, Spot was aboard the Enterprise-E with Data.

Spot first appeared in "Data's Day" as a male, long-haired Somali cat, played by Monster. In subsequent appearances, Spot was seen as a more common American short-hair orange tabby, but still as a male. It was only in the seventh season episode "Force of Nature" that Spot was first referred to as she. In "Genesis", she even gave birth. The Star Trek Encyclopedia jokingly suggests that Spot may be a shapeshifter or the victim of a transporter malfunction.

Data loved cats but Brent Spiner is noted as having a dislike for the creature. In the TNG relaunch novel Before Dishonor, Worf has assumed the role of caretaker for Spot after Data's death. Worf, after Spot assists with hunting down an alien infestation on the Enterprise, states that he finds her to be a warrior, who simply lulls people into a false confidence of a cat.