Cultural areas represent a useful concept that cross-fertilizes diverse fields in social sciences. Knowledge of how humans organize and relate their ideas and behavior within a society helps to understand their actions and attitudes towards different issues. However, the selection of common traits that shape a cultural area is somewhat arbitrary. What is needed is a method that can leverage the massive amounts of data coming online, especially through social media, to identify cultural regions without ad-hoc assumptions, biases or prejudices. In this work, we take a crucial step towards this direction by introducing a method to infer cultural regions based on the automatic analysis of large datasets from microblogging posts. Our approach is based on the principle that cultural affiliation can be inferred from the topics that people discuss among themselves. Specifically, we measure regional variations in written discourse generated in American social media. From the frequency distributions of content words in geotagged Tweets, we find the words' usage regional hotspots, and from there we derive principal components of regional variation. Through a hierarchical clustering of the data in this lower-dimensional space, our method yields clear cultural areas and the topics of discussion that define them. We obtain a manifest North-South separation, which is primarily influenced by the African American culture, and further contiguous (East-West) and non-contiguous (urban-rural) divisions that provide a comprehensive picture of today's cultural areas in the US.