The objective of this paper is to explore cultural tourism perceptions, practices, concerns and prospects among local residents, tourists and business representatives in the Cycladic Islands, specifically three sites (Andros, Syros and Santorini). The concept and framework of cultural sustainability are employed to analyze the variable interrelationships between culture and tourism in the development of cultural tourism and in overall local sustainability, from a bottom-up/destination perspective. The methodological approach was an on-site exploratory questionnaire survey, effectuated in the context of the SPOT Horizon 2020 EU project, on cultural tourism in the Cyclades. Our findings show that the role of culture as an actual tourism attraction and the potential for further growth in cultural tourism, and consequently local development, are broadly recognized. However, the role of tourism in cultural development, management and appropriation is viewed with a certain degree of trepidation and ambivalence. Culture and tourism emerge from the results of this research study as positively interlinked in the minds of the locals, the visitors and the entrepreneurs involved in cultural tourism and tourism more generally. Despite the fact that it is mostly privately driven, the culture–tourism relationship is viewed as holding great potential for all sides involved and for local cultural and overall sustainability.