We consider the problem of determining when the difference of two ribbon Schur functions is a single Schur function. We fully classify the five infinite families of pairs of ribbon Schur functions whose difference is a single Schur function with corresponding partition having at most two parts at least 2. We also prove an identity for differences of ribbon Schur functions and we determine some necessary conditions for such a difference to be Schur-positive, depending on the distribution of 1's and the end row lengths.