We adapt a method from mammalian comparative biology to study spatial cognition in relation to lifestyle. We compare members of the family Pitheciidae (titi monkeys, sakis, bearded sakis, and uakaris) to one another and to two cebid relatives, squirrel monkeys and owl monkeys. We review experimental studies that directly compare titis and squirrel monkeys in spatial tasks and social settings. Titis occupy small, defended home ranges and live in small groups comprising an adult male-female pair and young. In contrast, bearded sakis, uakaris, and squirrel monkeys, occupy large, undefended home ranges, move rapidly, and live in large groups. White-faced sakis illustrate an intermediate condition. Lab studies show that titis and squirrel monkeys differ in their use of visual information in travel tasks and in responsiveness to environmental novelty. Proximate sources of titis’ cautious, sedentary lifestyle include attention to contextual detail, preferences for familiar pathways and areas, behavioral inhibition, parasympathetic dominance, and adult heterosexual attachment bonds. A speculative scenario for the evolution of titis within the Pitheciidae is offered, in which spatial cognition is included as a factor. Further potential applications of this approach within the primate order are considered. We maintain that a holistic, biological, and evolutionary methodology is most likely to elucidate the underpinnings and form of complex cognition.