Recently, many programs have been funded to tackle Indigenous Australian smoking. This study assessed what challenges and unexpected responses could occur when developing anti-tobacco messages for Indigenous communities. A cross-sectional telephone survey of organizations involved in making anti-tobacco messages for the target population was conducted in 2012-2013. Open-ended questions explored cultural challenges to message development and unexpected outcomes. Responses were noted and these qualitative data were independently coded by two researchers using an inductive analysis. Non-parametric tests explored associations between organization orientation, whether target group feedback about messages was sought (pre-tests) and the presence of the above factors. The 47 organizations represented included: 22 Aboriginal Medical Services (AMS), 13 government organizations (GO), eight non-government organizations (NGO) and four universities. The response rate was 83%. Cultural challenges were reported equally by organizations oriented towards Aboriginal communities and those oriented towards the general population. Organizations conducting target group pre-tests of the messages were more likely to report cultural challenges (p = 0.002). Four main themes were revealed: the diversity of Aboriginal and Torres Strait Islander cultures; the selection of role models; conflicts and delays; and unexpected outcomes. Nearly 60% of organizations reported better-than-expected outcomes e.g. community appreciation and pride. A further 40% reported negative responses, e.g. messages being misunderstood or confronting. Cultural challenges and unexpected outcomes are reported by Australian organizations when developing anti-tobacco messages for Indigenous Australians warranting attention to improve the salience of anti-tobacco messages for Indigenous peoples.NB. In this paper, Indigenous Australians is a term used to refer to Aboriginal and Torres Strait Islander peoples, the first inhabitants of Australia. No offence is intended. The authors acknowledge and respect that Aboriginal and Torres Strait Islander people are diverse populations with different language and cultural groups.