Little String Theory (LST) is a still somewhat mysterious theory that describes the dynamics near a certain class of time-like singularities in string theory. In this paper we discuss the topological version of LST, which describes topological strings near these singularities. For 5 + 1 dimensional LSTs with sixteen supercharges, the topological version may be described holographically in terms of the N = 4 topological string (or the N = 2 string) on the transverse part of the near-horizon geometry of N S5-branes. We show that this topological string can be used to efficiently compute the half-BPS F 4 terms in the lowenergy effective action of the LST. Using the strong-weak coupling string duality relating type IIA strings on K3 and heterotic strings on T 4 , the same terms may also be computed in the heterotic string near a point of enhanced gauge symmetry. We study the F 4 terms in the heterotic string and in the LST, and show that they have the same structure, and that they agree in the cases for which we compute both of them. We also clarify some additional issues, such as the definition and role of normalizable modes in holographic linear dilaton backgrounds, the precise identifications of vertex operators in these backgrounds with states and operators in the supersymmetric Yang-Mills theory that arises in the low energy limit of LST, and the normalization of two-point functions.In this paper we focus on the most symmetric LSTs, which are 5 + 1 dimensional theories with sixteen supercharges (N = (1, 1) supersymmetry in six dimensions). These theories arise from decoupling limits of type IIA strings on ALE spaces (non-compact K3 manifolds that arise by blowing up the geometry in the vicinity of ADE singularities of compact K3 surfaces), or from decoupling limits of type IIB N S5-branes in flat space.The holographic description of these theories is given by string theory on the near-horizon geometry of N S5-branes, the CHS background [16]. The discussion above suggests that the N = 2 string on the CHS background is holographically dual to a topological version of the corresponding LST. In this paper we investigate this suggestion.Before taking any decoupling limits, the topological string computes various amplitudes which are protected by supersymmetry in the full type II string theory [9]. These correspond to the coefficients of specific terms in the low-energy effective action of the theory. It is interesting to ask what do correlation functions in the topological version of LST compute. In general, LSTs are known to have operators which are defined off-shell, and the physical observables are Green's functions of these operators. This is different from critical string theory, in which the observables are on-shell S-matrix elements. The discussion above suggests that there should be some sub-class of the correlation functions of the off-shell observables of LST which is topological in nature, and which is computed by the topological LST. One way to derive this sub-class is by taking a limit of the topological...