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.