The Neapolitan Mastiff is fearless and extremely protective of its home and family. They prefer to be with their family and to remain in and around the home at all times. The Neapolitan Mastiff rarely barks unless under provocation, renowned for sneaking up on intruders as opposed to first alerting them of their presence.

Neos, as a breed, are extremely intelligent dogs with a tendency to be independent thinkers. They learn quickly, which is both good and bad, since this guardian breed needs extensive proper socialization to learn to accept strangers, especially within the home; without proper early socialization and training, these dogs are likely to become aggressive towards strangers and unfamiliar dogs. Like with other breeds, forceful training methods, "alpha rolls", and a general "dominance" mentality will not work with these dogs, especially since it is difficult to try to physically dominate a dog that is so large as an adult; if you want a well mannered dog, prevent problems before they happen by using positive training methods, beginning socializing early, and continuing socializing throughout life.

The Neapolitan Mastiff is not a breed for most people, and certainly not a dog for beginners. As a general rule, Neapolitan Mastiffs are not appropriate for homes with small children, as Neos are large, powerful dogs and don't always know their own strength. Additionally, young children have young friends, and even with extensive socialization and training, Neapolitans will be wary of strangers and protective of their family, which can be disasterous for small children.