Styrene is an important commodity chemical used in polymers and resins, and is typically produced from the petrochemical feedstocks benzene and ethylene. Styrene has recently been produced biosynthetically for the first time using engineered Escherichia coli, and this bio-based route may represent a lower energy and renewable alternative to petroleum-derived styrene. However, the economics of such an approach has not yet been investigated. Using an early-stage technoeconomic evaluation tool, a preliminary economic analysis of bio-based styrene from C6-sugar feedstock has been conducted. Owing to styrene’s limited water solubility, it was assumed that the resulting fermentation broth would spontaneously form two immiscible liquid phases that could subsequently be decanted. Assuming current C6 sugar prices and industrially achievable biokinetic parameter values (e.g., product yield, specific growth rate), commercial-scale bio-based styrene has a minimum estimated selling price (MESP) of 1.90 USD kg−1 which is in the range of current styrene prices. A Monte Carlo analysis revealed a potentially large (0.45 USD kg−1) standard deviation in the MESP, while a sensitivity analysis showed feedstock price and overall yield as primary drivers of MESP.