Conventional fossil fuels are more and more regulated in terms of both engine-out emissions and fuel consumption. Moreover, oil price and political instabilities in oil-producer countries are pushing towards the use of alternative fuels compatible with the existing units. N-Butanol is an attractive candidate as conventional gasoline replacement, given its ease of production from bio-mass and key physico-chemical properties similar to their gasoline counterpart. A comparison in terms of combustion behavior of gasoline and n-Butanol is here presented by means of experiments and 3D-CFD simulations. The fuels are tested on a single-cylinder direct-injection spark-ignition (DISI) unit with an optically accessible flat piston. The analysis is carried out at stoichiometric undiluted condition and lean-diluted mixture for both pure fuels. Numerical simulations are carried out on the same operating points and a dedicated set of detailed chemistry simulations are used to accurately predict laminar flame speed for both gasoline and n-Butanol at selected engine-relevant conditions. Moreover, a method to accurately fit target results is presented and it is applied to obtain a polynomial form of laminar flame speed for both fuels. Mixture preparation and combustion development are carefully analyzed to explain the experimental evidence and to argument the differences between the two fuels, as well as the fuel-specific tolerance to mixture leaning. Finally, conclusions are drawn to summarize the obtained results and to outline the foreseen advantages of using n-Butanol as gasoline substitute in modern SI engines.